Objectives: To compare the efficacy of GnRH antagonist multiple dose protocol (MDP) with that of GnRH agonist long protocol (LP) in controlled ovarian hyperstimulation for in vitro fertilization in patients with high basal FSH (follicle stimulating hormone) level or old age, a retrospective analysis was done. Methods: Two hundred ninety four infertile women (328 cycles) who were older than 41 years of age or had elevated basal FSH level (> 8.5 mIU/mL) were enrolled in this study. The patients had undergone IVF-ET after controlled ovarian hyperstimulation using GnRH antagonist multiple dose protocol (n=108, 118 cycles) or GnRH agonist long protocol (n=186, 210 cycles). The main outcome measurements were cycle cancellation rate, consumption of gonadotropins, the number of follicles recruited and total oocytes retrieved. The number of fertilized oocytes and transferred embryos, the clinical pregnancy rates, and the implantation rates were also reviewed. And enrolled patients were divided into three groups according to their age and basal FSH levels; Group A - those who were older than 41 years of age, Group B - those with elevated basal FSH level (> 8.5 mIU/mL) and Group C - those who were older than 41 years of age and with elevated basal FSH level (> 8.5 mIU/mL). Poor responders were classified as patients who had less than 4 retrieved oocytes, or those with $E_2$ level <500 pg/mL on the day of hCG injection or those who required more than 45 ampules of exogenous gonadotropin for stimulation. Results: The cancellation rate was lower in the GnRH antagonist group than in GnRH agonist group, but not statistically significant (6.8% vs. 9.5%, p=NS). The amount of used gonadotropins was significantly lower in GnRH antagonist group than in agonist group ($34.8{\pm}11.3$ ampules vs. $44.1{\pm}13.4$ ampules, p<0.001). The number of follicles > 14 mm in diameter was significantly higher in agonist group than in antagonist group ($6.7{\pm}4.6$ vs. $5.0{\pm}3.4$, p<0.01). But, there were no significant differences in clinical pregnancy rate (24.5% in antagonist group vs. 27.4% in agonist group, p=NS) and implantation rate (11.4% in antagonist group vs. 12.0% in agonist group, p=NS) between two groups. Mean number of retrieved oocytes was significantly higher in GnRH agonist LP group than in GnRH antagonist MDP group ($5.4{\pm}3.5$ vs. $6.6{\pm}5.0$, p<0.0001). But, the number of mature and fertilized oocytes, and the number of good quality (grade I and II) and transferred embryos were not different between two groups. In each group A, B, and C, the rate of poor response did not differ according to stimulation protocols. Conclusions: In conclusion, for infertile women expected poor ovarian response such as who are old age or has elevated basal FSH level, a protocol including a controlled ovarian hyperstimulation using GnRH antagonist appears at least as effective as that using a GnRH agonist, and may offer the advantage of reducing gonadotropin consumption and treatment period. However, much work remains to be done in optimizing the GnRH antagonist protocols and individualizing these to different cycle characteristics.
Pyoderma gangrenosum is uncommon neutrophilic dermatosis characterized by richness of the mature neutrophilic polynuclear dermal infiltrate. Pyoderma gangrenosum is associated with variable diseases, most commonly inflammatory bowel disease, hematological diseases, malignancies, but it is reported rarely in rheumatoid arthritis. We report a case of pyoderma gangrenosum in rheumoid arthritis patient. A 50-year-old woman admitted to our hospital due to painful pretibial ulcerative skin lesions. She had been treated as rheumatoid arthritis for 8 years. At admission, body temperature was $36.5^{\circ}C$ and other vital sign was unremarkable. Physical examination revealed right pretibial ulceration, multiple pustules on left pretibial area and both palms. Laboratory studies revealed WBC count 7,600/uL (neutrophils 60.3%, eosinophil 3.2%), hemoglobin 11.4 g/dL, platelet count 319,000/uL, ESR 65 mm/hour. Other lab findings were also unremarkable. Skin biopsy was done, which showed dense dermal infiltrate of neutrophils and wound culture were negative. By 8 weeks after systemic high dose corticosteroid (1 mg/kg/day), cyclosporine A (5 mg/kg/day), sulfasalazine 2 g therapy, symptoms and skin ulceration were being improved. Without skin relapse, she is followed up our hospital with low dose corticosteroid and sulfasalazine.
The pharmacokinetics of erythromycin (EM) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using LC/MS/MS. After single- or multiple-dose administration of EM (50, 100, 200 mg/kg body weight and 50 mg/kg for 5 days) by oral route in olive flounder ($350{\pm}40g$, $22{\pm}0.5^{\circ}C$), the concentration in the serum was determined at 1, 3, 6, 9, 24, 72, 120, 168, 264, 360, 504 and 720 h post-dose. The kinetic profile of absorption, distribution and elimination of EM in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) following oral administration of 50, 100 and 200 mg/kg b.w. and 50 mg for 5 days. EM was $165.3hr^*{\mu}g/m{\ell}$ ($C_{max}$, $34.63{\mu}g/m{\ell}$; $T_{max}$, 1.56 hr), $212.8hr^*{\mu}g/m{\ell}$ ($C_{max}$, $60.38{\mu}g/m{\ell}$; $T_{max}$, 3.99 hr), and $592.37hr^*{\mu}g/m{\ell}$ ($C_{max}$, $63.01{\mu}g/m{\ell}$; $T_{max}$, 4 hr), respectively. The results of this study related to dosage and ${\mu}{\cdot}$withdrawal times could be used for prescription of EM in field for the treatment of bacterial diseases in olive flounder.
Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.
To investigate the exposure effect of benzene, we measured airborne benzene as external doses, uninary tt-muconic acid as an internal dose of benzene exposure and analyzed the relationship between tt-muconic acid concentration and benzene exposure. The study population of eight businesses included 157 workers(87 workers in field; exposure group, 70 workers in board; control group) who produce or use benzene in petrochemical industry. The concentrations of airborne benzene were evaluated by personal samples and urine was sampled at the pre and end shift. Urinary t,t-muconic acid as internal dose was to analyze the relationship with airborne benzene. The geometric means(GM) of airborne benzene was 0.0231 ppm(range ND-1.0471 ppm) in exposure group and 0.0147 ppm(range ND-0.3162 ppm) in control group. The geometric means(GM) of urinary t,t-muconic acid at end-shift was $196.8{\pm}2.23{\mu}g/g$ creatinine in exposure group and $149.2{\pm}2.08{\mu}g/g$ creatinine in control group. There was significant correlation between the airborne concentration of benzene and the urinary concentration of t,t-muconic acid( r=0.711, p<0.01). From the results of stepwise multiple regression analysis about t,t-muconic acid at end-shift, significant independents was airborne benzene. In this study, there were significant correlation between the urinary concentration of t,t-muconic acid and the airborne concentration of benzene. More extensive studies ruling out healthy worker effect is needed.
Aucubin, an iridoid glucoside which was previously reported to exhibit liver-protective activities against $CCl_4$ and ${\alpha}-amanitin$ induced liver damages, was subject to toxicological studies. To measure the lethal dose, the doses of 100mg/kg, 300mg/kg, 600mg/kg and 900mg/kg were administered intraperitoneally to experimental mice. No death was observed 24 hrs later, but serum GOT and alkaline phosphatase activities were deceased slightly at the doses of 300mg to 900mg/kg, and the triglyceride contents were slightly increased. To investigate acute toxicity of aucubin itself, multiple dosages(20 mg/kg, 40 mg/kg and 80 mg/kg for four times a week) were injected intraperitoneally into mice, then serum enzymes activities and chemistries were assayed; no significant change of the enzyme activities of alkaline phosphatase, GPT, GOT in the test groups were observed in comparison with those of the control group, and the contents of triglyceride, glucose, urea nitrogen and total proteins in the test group serums appeared to be almost same levels as those of the control group were. Histological examiation on liver biopsy samples indicated no gross changes between the control group and the test group were noted. Therefore, aucubin appears to be apparently low toxic substance and its minimum lethal dose in mouse seems to be more than 0.9 g.
We have developed a device for recording biological data by inserting three electrodes and a needle with an angular velocity sensor into the moth for the purpose of measuring the electromyogram of the flapping and the corresponding lift force. With this measurement, it is possible to evaluate the moth-physiological function of moths, and the amount of pesticides that insects are exposed to (currently LD50-based standards), especially the amount of chronic low-concentration exposure, can be reduced the dose. We measured and recorded 2-channel electromyography (EMG) and angular velocity corresponding to pitch angle (pitch-like angle) associated with wing flapping for 100 sweet potato hawkmoths (50 females and 50 males) with the animals suspended and constrained in air. Overall, the angular velocity and amplitude of EMG signals demonstrated high correlation, with a correlation coefficient of R = 0.792. In contrast, the results of analysis performed on the peak-to-peak (PP) EMG intervals, which correspond to the RR intervals of ECG signals, indicated a correlation between ΔF fluctuation and angular velocity of R = 0.379. Thus, the accuracy of the regression curve was relatively poor. Using a DC amplification circuit without capacitive coupling as the EMG amplification circuit, we confirmed that the baseline changes at the gear change point of wing flapping. The following formula gives the lift provided by the wing: angular velocity × thoracic weight - air resistance - (eddy resistance due to turbulence). In future studies, we plan to attach a micro radio transmitter to the moths to gather data on potential energy, kinetic energy, and displacement during free flight for analysis. Such physiological functional evaluations of moths may alleviate damage to insect health due to repeated exposure to multiple agrochemicals and may lead to significant changes in the toxicity standards, which are currently based on LD50 values.
Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.
In vitro dissolution test and pharmacokinetic study in human volunteers were conducted to evaluate the pharmacokinetic characteristics of 150 mg furbiprofen sustained-release capsule (FPSR-150). As a reference product, 50 mg flurbiprofen conventional-release capsule (FPCR-50) was used. Dissolution tests of two products were run using the paddle method in 450 : 540 (v/v %) mixture of simulated gastric and intestinal fluids (K.P. VI) by adjusting medium pH according to time. FPCR-50 was dissolved very rapidly, and it took about 1.5 hr for FPCR-50 to be dissolved over 90%, whereas 15 hr for FPSR-150. Also, in pharmacokinetic study, ten healthy male volunteers were administered one capsule of FPSR-150 or two capsules of FPCR-50 (FPCR-l00) with randomized two period cross-over study. Significant differences between FPCR-l00 and FPSR-150 were found in mean times to reach peak concentration, mean resident times and mean terminal phase halflives, while not in AUC/Dose (Student's t-test). In ANOVA for AUC/Dose to compare the bioavailabilities of two FP products, there was no significant difference. From the comparison of the simulated steady-state plasma concentration-time curves following multiple medications of FPCR-50 (3 capsules a day, dosing interval=8 hrs) and FPSR-150 (1 capsule a day) based on the above results obtained from single doses of two FP products, it was noted that the medication of FPSR-150 is more useful in clinical application rather than FPCR-50.
Purpose: The purpose of this study was to identify the mediating effect of confidence for drug calculation in the relationship between interest in medication and drug calculation competency using learning style. Methods: Participants in this study were 421 nursing students from Busan and Kyungnam province. The scales of learning style, interest in medication, importance of perception, confidence for drug calculation, and drug calculation competency for nursing students were used in this study. Descriptive statistics, $X^2$-test, t-test, Pearson correlation coefficient, and stepwise multiple regression were used for data analysis. Results: Learning styles of the participants were diverger 19.0%, accommodator 30.9%, converger 21.1%, and assimilator 29.0%. The drug dose calculation competency of participants was relatively low with a mean score 66.73. There were significant positive correlations among drug dose calculation competency, interest in medication (r=.31, p<.001), and confidence for drug calculation (r=.44, p<.001). Confidence for drug calculation was a moderator between interests in medication and drug calculation competency. Conclusion: Based on the result of this study, confidence for drug calculation promoting strategy such as medication reconciliation and various learning technology for improving drug calculation competency are needed.
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