Synopsis We invesigated Mg absorption in the intestine, and pregnancy-associated changes in Mg absorption by the rat everted gut sac method. Heavy ion beam accelelated by ring-cyclotron was irradiated to a titanium target and the radioactive multitracer solution which includes ²⁸Mg was made. 9 weeks old female Wistar rats (non-pregnancy, 6~20th day of the pregnancy) were fasted overnight and anesthetized. Four segments of the intesitine were isolated and everted to prepare sac specimens with mucosa outside. Each specimen was filled with multitracer solution and was immersed in the same solution. After incubation the multitracer solutions in both of inside and outside the sacs were removed. The radio activity of the each sample was determined by gamma-ray spectrometry. In non-pregnant state, the active transport of Mg from mucosal side into serosal side exists only in colon. This active transport of Mg in colon during pregnancy was significantly decreased than in non-pregnant state. The mechanism and importance of the decrease in Mg absorption during pregnancy are still unclear. In humans, the intracellular and extracellular Mg concentrations decrease with the normal pregnancy course, especially in preeclampsia. The association between the changes in active Mg absorption during pregnancy and the pathogenesis should be clarified as early as possible. [Adv Obstet Gynecol, 56(2) : 53-61, 2004(H16.5)]

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Synopsis To evaluate the possible relationship between the follicular inhibins and fertilizing capacity of the human oocyte, this study was carried out in women undergoing assisted conception. Follicular fluids (FFs) were collected from individual follicles during oocyte retrieval for in vitro fertilization with the informed consent. The concentrations of dimeric inhibin A, inhibin B in FFs were measured using a solid phase sandwich enzyme linked immunosorbent assays and the concentrations of estradiol, testosterone, and progesterone in FFs were measured using RIA. Hormone concentrations were compared with FFs volume, oocyte quality and embryo development.
Inhibin A concentrations in FFs did not correlate with the volume, whereas inhibin B concentrations in FFs negatively correlated with the volume. The mean concentration of inhibin B was significantly higher in FFs containing immature oocyte than that of FF containing mature oocyte. FFs from small immature follicles in which we could not get oocyte showed high concentrations of inhibin B. The mean concentration of inhibin B was significantly higher in FFs containing non-fertilized oocyte than that of FF containing fertilized oocyte. FFs containing oocyte which was revealed to be high quality embryo after subsequent development showed lower concentrations of inhibin B compared with FFs containing oocyte which was revealed to be a low quality embryo. The significant correlation between the concentrations of inhibin A and progesterone in FFs was observed, while no significant correlation was found between the concentrations of inhibin B and progesterone in FFs. The concentrations of inhibin B in FFs were significantly lower in mature follicles including oocytes with fertilizing capacity than those in immature follicles. On the other hand, the concentrations of inhibin A in FFs were correlated with the concentrations of progesterone in FF, whereas they did not show any relationship with oocyte maturity and its fertilizing capacity. These results indicate that the concentrations of inhibin B in FFs might be a potential predictor in the assessment of oocyte quality and fertilizing capacity. [Adv Obstet Gynecol, 56 (2) : 62 -69 , 2004 (H16.5)]

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Synopsis A chronic imbalance in the bone-remodeling process results in a net excess of bone resorption over bone formation, producing a loss of bone mass and alteration of architecture. Available antiresorptive agents increase bone mineral density (BMD) and reduce fractures in women with postmenopausal osteoporosis. Bisphosphonate and estrogen are effective in the management of postmenopausal osteoporosis, but the efficacy and safety of alendronate added to ongoing hormone replacement therapy (HRT) are unknown. The objective of the present study was to evaluate the effects of alendronate added to ongoing HRT on BMD and on biochemical markers of bone turn over in postmenopausal women with low BMD.
A total of 26 postmenopausal women with low BMD, who had been receiving HRT for at least 4 months, received either HRT alone (n=16) or HRT plus alendronate (5mg/day, n=10).
A 8-month treatment with alendronate plus HRT resulted in a significant increase in lumbar spine BMD compared with HRT alone (p<0.05). The postmenopausal women with HRT plus alendronate were divided into two groups, the Greater-BMD increase (†3.5%) and Less-BMD increase (<3.5%) group, based on the median variation in BMD (3.5%) at 8-month treatment. The pretreatment deoxypyridinoline (DP) levels and the variation in DP levels at 8-month treatment were significantly larger in the Greater-BMD increase group than the those in Less-BMD increase group , respectively (p<0.05) .
This study demonstrated that alendronate added to HRT significantly increased BMD at the lumbar spine in postmenopausal women with low BMD despite ongoing HRT, and that DP levels at pretreatment might have a predictive value in evaluating whether BMD are increased by addition of alendronate to ongoing HRT. [Adv Obstet Gynecol, 56(2) : 70-76, 2004(H16.5)]

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Synopsis Muroto deep sea water, which is obtained from about 300 m below sea level offshore the Muroto Promontory and is widely sold as drinking water after desalination, contains many kinds of minerals, especially an abundance of magnesium. The aim of this study is to investigate the effect of Muroto deep sea water on bone metabolism when ingested by perimenopausal women with osteopenia or osteoporosis.
Eighteen perimenopausal women with osteopenia or osteoporosis (49-62 years old) were recruited. Twelve women took 500ml of Muroto deep sea water daily for 12 weeks (supplementation of magnesium 100mg/day ; drinking group), and 6 age-matched women abstained to be treated as the control (control group). Electrolytes (Ca, Mg, P), biochemical markers of bone metabolism (bone specific ALP, osteocalcin and NTx/Cre) and calcium regulating hormones (intact-PTH, 1.25-(OH)₂Vit.D and calcitonin) in blood or urine were measured in both groups every 4 weeks. Bone mineral density at the lumbar spine (L2-4) was assessed at the beginning and the end of the 12 weeks.
In the drinking group, serum Mg concentration was increased significantly compared with the baseline level or control group at the 4th week, but there was no significant change at the 8th or 12th week. Urinary Mg/Cre concentration was significantly increased compared with baseline at the 4th, 8th and 12th weeks in the drinking group, and at the 4th and 12th weeks in the control group. No significant change in Ca and P concentration was observed in serum or urine. Serum bone specific ALP did not show significant change during the period. Serum osteocalcin concentration at the 12th week was significantly decreased compared with baseline level in the drinking and control group; furthermore, the percent change in the drinking group was significantly lower than in the control. Urinary NTx/Cre concentration at the 12th week did not different from baseline level in the drinking group, but the percent change in the drinking group was significantly lower than in the control. Serum calcium regulating hormones were unchanged. No other side effect was observed during or after treatment. Bone mineral density did not show any significant change in either group.
Taking Muroto deep sea water for 12 weeks in perimenopausal women with osteopenia or osteoporosis led to a decrease in the biochemical markers of bone resorption and formation, resulting in suppressed bone turnover. These findings indicated the possibility that long-term ingestion of Muroto deep sea water may have a suppressive effect of decreasing bone mineral density. [Adv Obstet Gynecol, 56(2) : 77-84, 2004(H16.5)]

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Synopsis We report a case of Wunderlich syndrome, complex of didelphic uterus, blind hemivagina and ipsilateral renal agenesis. This syndrome is one of the rare uterine malformations and is often difficult to have an accurate preoperative evaluation. The patient was a 20-year-old nulliparous woman, with repeated abdominal pain and low-grade fever, which persisted on and off from menarche. Buldging of the left-sided lateral vaginal wall was found in the pelvic exam. Trasvaginal ultrasonography revealed fluid retention inside the vaginal wall and two separate horns of uterine corpus. Magnetic resonance imaging of the pelvis confirmed the finding of didelphic uterus with blind hemivagina, and intravenous pyelography added the finding of ipsilateral renal agenesis. She underwent laparoscopic exploration and resection of vaginal septum, and purulent retained material was drained from her blind vagina. The removed vaginal wall contained both columnar and squamous epithelium on the obstructed side. This histologic finding proved this case Wunderlich syndrome, in which the hemato- or pyocolpos was derived from cervical glandular epithelium. The symptoms of the patient were completely relieved and have not recurred postoperatively for 6 months. Recent reports and studies have proven that the appropriate treatments for this type of malformation are laparoscopic exploration and resection of vaginal septum, instead of hemihysterectomy with ipsilateral hemicolpectomy, which had been performed in the past years. Early accurate diagnosis followed by appropriate treatment not only relieves symptoms, but also avoids complications such as endometriosis or chronic pelvic inflammation, which decrease the reproductive potential and occasionally require more extensive surgical intervention. [Adv Obstet Gynecol, 56(2) : 85-90, 2004(H16.5)]

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Synopsis Serum cholinesterase (ChE) or pseudocholinesterase has been recognized as an enzyme that hydrolyzes choline esters to choline and organic acid, and it can be found in the liver, blood, and various internal organs. This enzyme is generally accepted as being synthesized in the liver and has been routinely measured as a test of liver function and has been used as a preoperative parameter. Patients with low ChE generally have no signs or symptoms and can have a healthy life. However, when these patients must be injected with a muscle relaxant, such as succinylcholine, which is broken down by ChE, they may develop prolonged apnea because of the lack of this enzyme. Moreover, its' absence causes escalation of blood concentration of amino-ester type of anesthetics and eventually lead to convulsion. Thus, it is important to evaluate the levels of serum ChE. The cholinesterase activity in pregnant women is low and is about 70% of the normal range.
We had a patient who had absence of ChE. All other laboratory results were normal. The absence of ChE was just accidentally diagnosed when patient had serum level determination prior to elective cesarean section.
This case involves a 26 year-old woman G3P1 (1011) who was admitted in our hospital because of elective cesarean section at 37 weeks of gestation. Her fetus was in breech presentation and she had intramural myoma. Her serum cholinesterase was anomalously low at 2.0 IU/l (normal range=203~460 IU/l ; the substrate was 5-Methyl-2-thenoylthiocholine-iodine). The spinal anesthetic agent was changed from amino-ester type (usual choice) to amino-amide type. Surgery was uneventful. If we had to do emergency cesarean section under general anesthesia, depolarizing relaxant will be avoided.
The usual abnormality with ChE is very low level, hence this case was unusual because of the absence of ChE. We assumed that she is an atypical form of human ChE or deficiency of ChE. After obtaining informed consent for DNA analysis, we collected whole blood samples, and extracted white-blood cell DNA. Exons 2, 3 and 4, which encode the entire mature protein of ChE, were individually amplified by polymerase chain reaction (PCR). After confirming the sizes and homogeneity of the PCR products, we performed direct sequencing of the entire coding region of the ChE gene. Analysis of ChE gene revealed two-point mutations at nucleotides 1615 (exon 3) and 1543 (exon4), and both were homozygous. We suppose that these two homozygous mutations caused a decrease in ChE activity. Furthermore, we performed DNA analysis of her family because of this finding, with the probability of hereditary ChE deficiency or low ChE. There are very few reports of pregnancy complicated with ChE deficiency. Moreover, the two-point mutations which are homozygous have not been reported.
In conclusion, it is very important to determine ChE prior to administration of any anesthetic agent in order to avoid complications associated with cholinesterase deficiency. [Adv Obstet Gynecol, 56(2) : 91-98, 2004(H16.5)]

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