• Toxicological Research
• /
• v.29 no.1
• /
• pp.53-60
• /
• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Korean Journal of Clinical Laboratory Science
• /
• v.43 no.1
• /
• pp.1-5
• /
• 2011

The infection rate of syphilis is still increasing in the world especially in developing countries and the infection is often seen in large amounts of clinical specimens. For the diagnosis of this disease, Rapid Plasma Reagin (RPR)/Venereal Disease Research Laboratory (VDRL) has still been used as one of major primary methods to diagnose syphilis even though the test readings are somewhat subjective with high false positive rates. Recently, the automatic ARCHITECT Syphilis TP, which is based on the detection of the TP-specific antibodies, has been introduced in many laboratories. Therefore, the clinical assessment of the method is needed to provide primary diagnosis of syphilis at the moment. We evaluated 3 different manual rapid kits and ARCHITECT Syphilis TP comparing with RPR/FTA-ABS and analysed their diagnostic properties. From February 2006 to April 2008, 203 positive and 250 negative specimens, obtained from Chungbuk National University Hospital were used for the evaluation. In the evaluation between manual rapid kits, their specificities were as high as 99.2 ~ 99.6% while their sensitivities were observed with little differences; 98.0% (199/203) for Kit A, 96.6% (196/203) for Kit B, and 97.4% (197/203) for Kit S. In the case of ARCHITECT Syphilis TP test, it showed 100% specificity (250/250) and 98.5% sensitivity (249/250). Kappa values comparing with RPR/FTA-ABS were 0.978 for Kit A, 0.964 for Kit B and Kit S, and 0.987 for ARCHITECT Syphilis TP. From our evaluation, we found out that manual rapid tests and ARCHITECT Syphilis TP have very good clinical accuracies and high kappa agreements with RPR/FTA-ABS. Due to its automation and quick simultaneous diagnosis with another serological markers, we suggest that the ARCHITECT Syphilis TP is one of best suitable method for the primary diagnosis of syphilis and that it might be able to replace RPR method in the laboratories.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.12 no.3
• /
• pp.241-246
• /
• 2008

Purpose: To study of difference among primary aldosteronism patients and normal groups and essential hypertension patients and to confirm aldosterone/plasma renin activity ratio increase in secondary hypertension group which was diagnosed as primary aldosteronism. Materials and method: 1. Period: from April 2006 to March 2008. 2.Targets: 901 patients who visited seoul national university bundang hospital. 3. Groups: we divided by three groups. (normal group (n=147), essential hypertension (n=709), primary aldosteronism (n=45)) 4. Then calculated aldosterone/plasma renin activity ratio. 5. We used ROC curve to measure sensitivity and specificity. Results: 1. normal groups aldosterone/plasma renin activity ratio: $52.8{\pm}52.46$ essential hypertension patients aldosterone/plasma renin activity ratio: $171.04{\pm}291.56$ primary aldosteronism patients aldosterone/plasma renin activity ratio: $2325{\pm}2200$. 2. Aldosterone/renin ratio was significant in comparing each groups (p<0.001). 3. The sensitivity was 91.1% and the specificity was 92.4% when cut off of aldosterone/renin ratio was 485. Conclusion: It was confirmed that aldosterone/plasma renin activity ratio in primary aldosteronism was higher than normal group. According to this result, we can tell that aldosterone/ plasma renin activity ratio is very useful in diagnosis of primary aldosteronism.

• Korean Journal of Veterinary Research
• /
• v.35 no.3
• /
• pp.603-613
• /
• 1995

Plasma progesterone($P_4$) assay has been introduced to apply to the differential diagnosis of reproductive disorders and the monitoring of responses of ovarian dysfunction to $PGF_2{\alpha}$ or GnRH treatment in the 204 postpartum and postinsemination subestrus dairy cows. 1. The incidence rate of reproductive disorders in 204 subestrus cows, diagnosed by palpation per rectum and plasma $P_4$ determination using 'Two sample test'(Day 0+Day 10) were as follows; silent heat or error of estrus detection 110(53.9%), persistent corpus luteum 26(12.7%), follicular cyst 16(7.8%), inactive ovary 12(5.9%), luteal cyst 11(5.4%), granulosa cell tumor of ovary 1(0.5%), fetal mummification 1(0.5%), endometritis 15(7.4%) and pyometra 12(5.9%), respectively. 2. After the $PGF_2{\alpha}$ treatment to the 76 cows with silent heat or error of estrus detection, persistent corpus luteum, or luteal cyst, plasma $P_4$ concentrations at day 3 post treatment using 'Two sample test'(Day 0+Day 3) remained low(<1.0ng/ml) in all 76 cows. Therefore all 76 cows responded positively to $PGF_2{\alpha}$ treatment. Seventeen cows with follicular cyst or inactive ovary were treated with GnRH. All 7 cows with follicular cyst and 4 cows with inactive ovary remained high($${\geq_-}1.0ng/ml$$) a plasma $P_4$ concentrations at day 12 post treatment using 'Two sample test'(Day 0+Day 12), but 6 cows with inactive ovary remained low(<1.0ng/ml) a plasma $P_4$ concentrations. Therefore all 7 cows with follicular cyst and 4 cows with inactive ovary responded positively, but 6 cows with inactive ovary responded negatively to GnRH treatment. 3. The mean days from treatment to first service, number of cows conceived on first service(%), mean number of services per conception, mean days from initial treatment to conception, and mean number of cows conceived by 100 days post treatment(%) were 5.0 and 26.2 days, 45(59.2%) and 6(35.3%) cows, 1.5 and 1.7 services, 13.6 and 22.6 days, and 62(81.6%) and 9(52.9%) cows in group of $PGF_2{\alpha}$ and GnRH treatment, respectively. These results indicated that plasma $P_4$ assay was practical as an aid to diagnosing reproductive disorders and to monitoring responses of ovarian dysfunction to $PGF_2{\alpha}$ and GnRH treatment in subestrus cows.

• Korean Journal of Biological Psychiatry
• /
• v.12 no.2
• /
• pp.189-195
• /
• 2005

Objects:Some studies have suggested that brain-derived neurotrophic factor(BDNF), one of the most important neurotrophins, is involved in pathophysiology of depression and suicide. This study was performed to determine whether there is an abnormality in plasma BDNF concentration in suicidal attempters. Methods:The subjects were 71 suicidal attempters who visited emergency rooms in multi-medical centers. All subjects had been interviewed by using Structured Clinical Interview for DSM-IV(SCID), Hamilton Depression Rating Scale(HDRS), Young Mania Rating Scale(YMRS), and Positive And Negative Syndrome Scale(PANSS). The severity of the suicidal behavior was measured by Lethality of Suicide Attempt Rating Scale(LSARS) and Risk-Rescue Rating(RRR) system. Seventy-one age, sex, and diagnosis matched non-suicidal psychiatric patients who were consecutively admitted to a psychiatric ward during the same period recruited as psychiatric controls. They were drug-naive or drug-free at least more than 2 months. In addition, 80 healthy controls were randomly selected as normal controls. Plasma BDNF level was measured by the enzyme linked immunosorbent assay(ELISA) methods. Results:In overall F-test, differences of the plasma BDNF levels among the groups were statistically significant(F=20.226, p<0.001). In the multiple comparisons(Scheffe), while mean levels of plasma BDNF between normal controls and non-suicidal psychiatric patients were similar(p=0.984), the BDNF levels of suicidal attempters were lower than those of other two groups(p<0.001). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal attempters. Conclusion:These results suggest that reduction of plasma BDNF level is related to suicidal behavior and BDNF level may be a biological marker of suicidal behavior.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.25 no.1
• /
• pp.29-33
• /
• 2021

Purpose Plasma renin activity (PRA) test is important for the diagnosis of primary aldosteronism. PRA is an easily deformed substance in vitro and affected by temperature changes. Laboratory of ASAN medical center has consistently found that there was a difference between the initial and re-experimental results. We compared and analyzed the differences in PRA test results according to the sample storage status. Materials and Methods The measurement of PRA was performed by using the radioimmunoassay. From August to September 2020, 43 PRA re-test samples were tested with different sample storage condition. The first group was re-examined by freezing the plasma-separated samples at -18℃, and the second group was re-examined with refrigerated EDTA sample. Also, additional tests were conducted on 13 PRA samples to verify the effect on thawing temperature differences in plasma-separated samples. The same samples were divided into two parts and stored frozen at -18℃, respectively, and thawing samples in room temperature and those in refrigerator were were conducted. Each result was compared and analyzed based on the initial experimental results. Results The results of re-examination after frozen storing plasma separation samples showed a lower correlation than the results of re-examination with EDTA plasma samples in refrigerator. When calculating the percentage based on the initial test results, the average percentage of each was 404.9% and 133.8%. The correlation coefficient was also R=0.8501 and R=0.9966, respectively, showing a higher correlation between plasma in the refrigerated sample EDTA tube. In comparison experiments with differences in thawing temperature, average percentage of the results of initial test and room temperature thawing was 94.3% and the average percentage of the results of refrigerated thawing was 88.0%. After again freezing the sample, the average percentage of the second room temperature thawing result is 107.5%, and the second refrigerated thawing group is 112.7%. Both groups showed an increase from first thawing. Conclusion A comparative analysis of retesting according to differences in sample storage methods in PRA tests showed a higher correlation between the results of retesting of the refrigerated EDTA plasma. And repeated freezing and melting of plasma separation samples, regardless of temperature during defrosting, has been shown to affect results. Therefore, retest of PRA should re-collect plasma from original EDTA plasma to increase reproducibility.

• Journal of Korean Neurosurgical Society
• /
• v.30 no.12
• /
• pp.1435-1438
• /
• 2001

A case of nonsecretory multiple myeloma in a 66 year-old-woman is reported. At first, she complained severe neck pain and radiologic finding showed C2 pathologic fracture. She complained severe low back pain 4 month later and L1 compression fracture was found. The lumbar MRI showed a 1.4cm-sized round enhancing lesion in the body of T12. Bone marrow aspiration biopsy at L1 spine showed a few polymorphous and small nests of mononuclear cell. L1 lamina bone biopsy showed many abnormal plasma cells. Pathologic diagnosis was multiple myeloma. However, plasma electrophoresis and protein immunoelectrophoresis of serum and urine of patient were normal. So, it is a nonecretory multiple myeloma case and the incidence of nonsecretory multiple myeloma is known to about 1% of all multiple myeloma.

• Journal of Veterinary Clinics
• /
• v.28 no.1
• /
• pp.159-162
• /
• 2011

Three cats with 2 weeks to 1 month history of drooling, halitosis, difficulty eating and pain on opening the mouth were presented to local animal hospitals. On physical examination, the gingiva was swollen, bright red and very painful with bilaterally symmetric pattern. Surgically excised abnormal gingival biopsy samples were requested for diagnosis. Histopathologically, gingival epithelium showed severe hyperplasia and ballooning degeneration. Moderate to severe infiltration of lymphocytes and plasma cells were presented in lamina propria. Immunohistochemically, inflammatory cells of the samples demonstrated major positive reactions for T lymphocytes. But some plasma cells also presented. According to polymerase chain reaction, tissues samples were negative for four kinds of feline viral pathogens. Based on the clinical, gross, histopathologic findings, these three cases were diagnosed as lymphoplasmacytic gingivitis in cats. In our best knowledge, this is the first case report in Korea.

• Journal of Korean Neurosurgical Society
• /
• v.46 no.2
• /
• pp.156-160
• /
• 2009

Solitary extramedullary plasmacytomas are isolated plasma cell tumors of soft tissue that typically do not metastasize. They are rare and account for 4% of all plasma cell tumors. To our knowledge, only 14 cases of solitary extramedullary plasmacytomas in the sphenoid sinus have been reported. A 32-year-old man presented to our department with complaint of ocular pain in the right eyeball and diplopia. Physical and neurological examinations revealed intact and prompt direct and indirect light reflexes in both pupils and limitation of extraocular muscle movement seen with the lateral gaze of the right eyeball. Magnetic resonance imaging suggested the presence of mucocele or mycetoma, therefore surgical resection was performed with endoscopic endonasal transsphenoidal approach. Histopathology was consistent with plasmacytoma. Systemic work-up did not show any evidence of metastasis and the sphenoid sinus was the sole tumor site, and therefore the diagnosis of solitary extramedullary plasmacytoma was confirmed. We report a rare case of solitary extramedullary plasmacytoma in the sphenoid sinus with successful treatment using the endoscopic endonasal transsphenoidal resection and adjuvant radiotherapy.

• YAKHAK HOEJI
• /
• v.55 no.1
• /
• pp.56-63
• /
• 2011

Fabry disease (FD) is an X-linked inborn error of glycoshpingolipid metabolism resulting from mutation in the enzyme ${\alpha}$-galactosidase A gene. The disease is an X-linked lipid storage disorder and the lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb-3). Measurement of Gb-3 in plasma has clinical importance for monitoring after enzyme replacement therapy for confirmed FD patients. Using electrospray ionization MS/MS we had developed, a simple, rapid, and highly sensitive analytical method for Gb-3 in plasma was used for the purpose of screening FD among high risk groups in Korean population. To date, no comprehensive results for FD screening have been performed and reported in Korea. We screened 1,100 outpatients from 13 hospitals (including clinics) to assess the incidence of FD among patients in high risk groups. For patients with borderline level amount of Gb-3, we repeated Gb-3 or performing complementary or confirmative assay with ${\alpha}$-Gal A activity and DNA mutaion analysis for confirmation diagnosis. Of 1,100 we diagnosed 3 FD with 2 classical type and 1 carrier (0.27%).