Coexistence of ovarian cancer and peritoneal tuberculosis: a case report.

Peritoneal tuberculosis (TB) is known to mimic advanced ovarian cancer. In this case report, we describe a unique case of ovarian cancer (endometrioid carcinoma grade 3) at the International Federation of Gynecology and Obstetrics (FIGO) stage IC1 with pulmonary and peritoneal TB, which was suspected preoperatively to be a coexistence of advanced ovarian cancer and pulmonary TB. A 68-year-old woman presented with a prominent abdominal mass and fever. Laboratory investigations, imaging, and sputum analysis indicated a probable diagnosis of ovarian cancer at FIGO stage IIIC, characterized by peritoneal dissemination and para-aortic lymph node metastasis, which was further complicated by coexisting pulmonary TB. Surgical management included total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Intraoperatively, the tumor was localized to the right ovary with significant peritoneal thickening and adhesions indicative of peritoneal TB. The surgery was completed without apparent complications. Postoperative histopathological evaluation confirmed grade 3 endometrioid carcinoma in the right ovary along with evidence of peritoneal TB. Given the extent of adhesions attributed to TB, lymph node dissection for staging was deemed challenging and was thus not pursued. Initiation of anti-TB treatment on postoperative day 2 resulted in marked regression of the preoperatively identified pulmonary nodules and para-aortic lymph node enlargement, suggesting their inflammatory origin from TB. Although postoperative chemotherapy is typically advocated for patients with stage IC1 endometrioid carcinoma grade 3, the patient opted against it. Consequently, no adjuvant therapy was administered and the patient remained under close observation.

Successful fertility preservation in stage II endometrial carcinoma with long-term progestin therapy: A case report.

Progestin therapy is a fertility-sparing treatment option for well-differentiated stage IA endometrioid carcinomas without myometrial invasion. Here, we present a case of successful pregnancy and live birth following long-term progestin therapy in a patient with stage II well-differentiated endometrioid carcinoma. A 30-year-old nulliparous woman with an unremarkable medical history presented with abnormal uterine bleeding. A 45 mm mass was identified in the lower uterine segment. An endometrial biopsy revealed grade 1 endometrioid carcinoma, leading to a diagnosis of stage II uterine corpus cancer based on hysteroscopic findings. The patient refused surgical treatment and underwent oocyte retrieval and cryopreservation at another hospital. A subsequent endometrial biopsy revealed a marked reduction in the Ki-67 index from approximately 60 % to less than 10 %, suggesting the possibility of a hormone-sensitive tumor. The patient persistently refused surgery. Therefore, progestin therapy with medroxyprogesterone acetate (MPA) at a dose of 400 mg/day was initiated as a temporary measure until the patient would accept surgery. The tumor gradually reduced in size and eventually disappeared after 9 months. The MPA therapy was discontinued uneventfully after 20 months. Sixteen months after the discontinuation of MPA therapy, atypical endometrial hyperplasia was detected, and a second round of MPA therapy was initiated. Progestin retreatment was successful and was discontinued at 6 months. Four years after the initial treatment, the patient achieved pregnancy through timed intercourse and delivered a healthy baby at 38 weeks of gestation.

Multidirectional Traction Method Using SURGICEL NU-KNIT and Surgical Suture in Robot-assisted Laparoscopic Surgery for Endometrial Cancer.

OBJECTIVE: To describe a novel approach to robot-assisted laparoscopic total hysterectomy (RH) for endometrial cancer that minimizes cancer sell spillage and develops a stable surgical field. DESIGN: Demonstration of the multidirectional traction method with narrated video footage. SETTING: Many reports have indicated that RH for endometrial cancer has the same or superior short-term results compared with conventional laparoscopic hysterectomy (LH), and the long-term prognosis is the same [1,2]. However, there are no randomized controlled trials of RH versus LH, and some previous reports [3] have suggested that RH has a worse prognosis than LH, so the long-term prognosis should be considered with caution. Factors that may affect the long-term prognosis include the use of uterine manipulators [4] and compression of the uterine body with robotic forceps without tactile sensation [3]. However, to the best of our knowledge, no surgical technique capable of avoiding these factors has been established yet. Herein, we report a multidirectional traction method using SURGICEL NU-KNIT (Ethicon; Johnson & Johnson Medical Ltd., Tokyo, Japan), a local hemostatic agent, and surgical sutures. INTERVENTION: Cut 2-0 Prolene (Ethicon; Johnson & Johnson Medical Ltd., Tokyo, Japan) with straight needles (ST-70) thread to 35 cm, stick a 1 × 2 cm piece of SURGICEL NU-KNIT, and make knots Fig. 1. This implement is used to puncture the incisional margins of the peritoneum and then the abdominal wall to bring the thread to the surface of the body, where it is grasped with forceps and fixed. By repeating this operation, multidirectional traction can be obtained Fig. 2. A manipulating suture is also attached to the uterus to minimize the compression of the uterine body with robotic forceps. CONCLUSION: The multidirectional traction method allows for reproducible stable surgical field development and minimizes cancer cell spillage by reducing uterine grasping by robotic forceps without the use of uterine manipulators.

Predictive score for postpartum hemorrhage in vaginal deliveries following frozen embryo transfer.

Objective: To develop a predictive score for life-threatening severe postpartum hemorrhage in vaginal deliveries following frozen embryo transfer. Materials and Methods: We conducted a retrospective cohort study of 315 singleton vaginal deliveries following frozen embryo transfer from 2017 to 2022. Severe postpartum hemorrhage was defined as hemorrhage exceeding 1500 mL. A predictive score was generated from maternal characteristics and obstetric complications before delivery. We performed multivariable logistic regression analysis using 2017-2020 data and assigned points to identified risk factors. The predictive score's accuracy was evaluated using 2021-2022 data. Results: A large baby (birth weight ≥3500 g), pre-delivery maternal body mass index ≥25 kg/m2, marginal or velamentous umbilical cord insertion, and history of postpartum hemorrhage were identified as risk factors. We assigned one point to a large baby, a pre-delivery maternal body mass index ≥25 kg/m2, and marginal or velamentous umbilical cord insertion, and two points to a history of postpartum hemorrhage. The sum of the points was defined as the predictive score. The cut-off was set at two points, with a score ≥2 points being the high-risk group and a score ≤1 point being the low-risk group. The predictive score demonstrated a sensitivity of 47.8%, specificity of 85.4%, positive predictive value of 45.8%, and negative predictive value of 86.4% in the 2021-2022 validation cohort. Conclusion: The predictive score identified severe postpartum hemorrhage in approximately half of the high-risk cases. Implementing measures such as autologous blood storage may facilitate rapid response during heavy bleeding and improve maternal prognosis.

The role of zinc on nutritional status, sarcopenia, and frailty in older adults: a scoping review.

BACKGROUND: Zinc (Zn) deficiency, malnutrition, sarcopenia, and frailty are prevalent among older adults and are prominent factors contributing to disability and mortality. OBJECTIVE: This scoping review was conducted to aid understanding of the extent and types of research addressing the role of Zn in nutritional status, sarcopenia, and frailty, among older individuals. METHOD: A systematic search was performed in August 2022 of 3 electronic databases (PubMed, Web of Science, and ProQuest) using predefined search terms. The review was conducted referring to the Arksey and O'Malley framework and PRISMA-ScR. RESULTS: The search retrieved 16 018 records, and a total of 49 studies were included in this review after the screening. Of those, 30 were based on dietary Zn intake, 18 on tissue Zn levels, and 1 on both. Most studies were based on cross-sectional data from community-dwelling older adults. Studies addressing the associations between Zn status and individual anthropometric and sarcopenia-related variables reported inconsistent results. However, most studies reported inverse associations between malnutrition, frailty, and Zn status. CONCLUSION: There was more consistent evidence of the relationship of Zn status with malnutrition, sarcopenia, and frailty rather than with individual nutritional parameters. Validated screening and assessment tools and criteria and prospective studies are required to elucidate the relationship of Zn with sarcopenia and frailty in the older population.

The impact of assisted reproductive technology on the risk of postpartum hemorrhage: Difference by the mode of delivery and embryo transfer.

AIM: The frequency of postpartum hemorrhage (PPH) is increasing in developed countries, and some reports suggest that assisted reproductive technology (ART) increases various perinatal complications, including PPH. We investigated whether the effect of ART pregnancies on the incidence of PPH is modified by the mode of delivery. METHODS: A retrospective cohort study was performed. We analyzed the medical records of 2914 pregnant women, including 411 pregnancies achieved by ART, which were delivered in our hospital from 2017 to 2020. PPH was defined as hemorrhage exceeding the 90th percentile of blood loss per the mode of delivery and number of fetuses. Multivariable logistic regression analysis was used to assess the association between ART and PPH. Propensity score-matched analyses were used to assess the difference in the incidence of PPH by the mode of delivery. RESULTS: As previously reported, multivariable logistic regression analysis showed that ART pregnancy is an independent risk factor for PPH. Propensity score-matched analysis for with and without ART showed a 3.39-fold higher incidence of PPH for ART pregnancy in the vaginal delivery group (p < 0.001). CONCLUSIONS: The effect of ART pregnancies on the incidence of PPH differed depending on the mode of delivery. Only in vaginal delivery, ART pregnancy increased the incidence of PPH.

Long-term vs short-term tocolysis with ritodrine hydrochloride: Propensity score-matched analysis.

OBJECTIVE: To investigate whether the short-term tocolysis protocol is as effective as the traditional long-term tocolysis protocol with intravenous ritodrine hydrochloride for preterm labour. STUDY DESIGN: This single-centre, retrospective, observational study was conducted at Kitano Hospital, Osaka, Japan between April 2016 and July 2021. At the study hospital, the management protocol for preterm labour after 26 weeks of gestation was changed from the long-term tocolysis protocol to the short-term tocolysis protocol in November 2019. This study compared patients managed with the two protocols, using propensity score analysis to overcome the potential weaknesses of a retrospective study. The primary outcome was the frequency of preterm birth before 34 weeks of gestation before and after the protocol was revised. The secondary outcomes were frequency of neonatal intensive care unit admission and frequency of neonatal chronic lung disease. RESULTS: The study population consisted of 82 patients managed by the long-term tocolysis protocol and 56 patients managed by the short-term tocolysis protocol. After propensity score-weighted adjustment, the median durations of intravenous ritodrine administration in the long-term and short-term protocols were 18 days and 3 days, respectively. Differences were not detected between the long-term and short-term protocols in terms of the frequency of preterm delivery before 34 weeks of gestation [23.7 % vs 21.6 %, risk ratio (RR) 0.91, 95 % confidence interval (CI) 0.47-1.77], frequency of neonatal intensive care unit admission due to preterm birth (49.5 % vs 39.3 %, RR 0.79, 95 % CI 0.53-1.19) and frequency of neonatal chronic lung disease (4.4 % vs 9.2 %, RR 2.07, 95 % CI 0.51-8.48). CONCLUSION: Using propensity score analysis, changing from the long-term tocolysis protocol to the short-term tocolysis protocol for the management of preterm labour after 26 weeks of gestation did not have a negative effect on the frequency of preterm birth or neonatal prognosis.

Unveiling microbiome profiles in human inner body fluids and tumor tissues with pancreatic or biliary tract cancer.

With the discovery of bacterial symbiosis in the tissues of various cancers, the study of the tumor microbiome is attracting a great deal of attention. Anatomically, since the gastrointestinal tract, liver, and pancreas form a continuous ductal structure, the microbiomes in the digestive juices of these organs may influence each other. Here, we report a series of microbiome data in tumor-associated tissues such as tumor, non-tumor, and lymph nodes, and body fluids such as saliva, gastric juice, pancreatic juice, bile, and feces of patients with pancreatic or biliary tract cancers. The results show that the microbiome of tumor-associated tissues has a very similar bacterial composition, but that in body fluids has different bacterial composition which varies by location, where some bacteria localize to specific body fluids. Surprisingly, Akkermansia was only detected in the bile of patients with biliary tract cancer and its presence was significantly associated with the performance of external biliary drainage (P = 0.041). Furthermore, we found that tumor-associated tissues and body fluids in deep inner body are mostly inhabited by unidentified and uncharacterized bacteria, suggesting that such bacteria may be potential targets for precision therapy in the future.

Protein Delivery to Cytosol by Cell-Penetrating Peptide Bearing Tandem Repeat Penetration-Accelerating Sequence.

Pas2r12 is comprised of a repeat of the penetration-accelerating sequence (Pas) (Pas2: FFLIG-FFLIG) and D-form dodeca-arginine (r12), a cell-penetrating peptide. Pas2r12 significantly enhances cytosolic delivery of cargo proteins, including enhanced green fluorescent protein and immunoglobulin G. Simply incubating Pas2r12 with cargo leads to their cytosolic tranlsocation. Cytosolic delivery of cargo by Pas2r12 involves caveolae-mediated endocytosis. In this chapter, we describe methods of cytosolic delivery of cargo using Pas2r12 and provide methods for investigating the cellular uptake pathway of cargo by Pas2r12.

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: Oral mucositis is a frequent and severe adverse event in patients undergoing chemoradiotherapy for head and neck cancers, especially grade 3 or 4 mucositis. Occurrence may result in drop-out from treatment, thereby reducing survival. We aimed to clarify the effectiveness and safety of rebamipide mouthwash for oral mucositis in patients with head and neck cancer receiving treatment. METHODS: We carried out a systematic review and meta-analysis of patients with head and neck cancer who were treated with rebamipide mouthwash. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trial Registry Platform. The primary outcome was the incidence of severe oral mucositis, and secondary outcomes were time from treatment start to onset of oral mucositis, the response rate of radiotherapy, and any adverse events. RESULTS: We included three studies comparing rebamipide versus placebo, all of which evaluating chemoradiotherapy induced oral mucositis. The chemotherapeutic agent was docetaxel in one study and cisplatin in the remaining two. Radiotherapy in each study consisted of 3D-conformal radiation therapy, intensity modulated radiation therapy and conventional radiation therapy, respectively. The calculated odds ratio was 0.29 [95% confidence interval (CI): 0.15 to 0.55], showing a positive association in the three studies between the incidence of grade 3-4 oral mucositis and chemotherapy for head and neck cancer. One study reported an onset of oral mucositis and the time to onset was 14.6 ± 6.4 days for the rebamipide group and 11.2 ± 4.4 days for placebo. One study reported a complete response of 8.3% for placebo and 16.7% for the rebamipide the group, and the partial response was 91.7 and 75.0%, respectively. Adverse events were reported in two studies to be 6.1 and 11.6% for placebo, and 19.4 and 26.0% in the rebamipide group, respectively. CONCLUSIONS: Rebamipide mouthwash is effective in the prevention of severe mucositis and stomatitis. However, evaluation of adverse events in observational studies are needed.

Oligoarginine-Bearing Tandem Repeat Penetration-Accelerating Sequence Delivers Protein to Cytosol via Caveolae-Mediated Endocytosis.

To facilitate the cytosolic delivery of larger molecules such as proteins, we developed a new cell-penetrating peptide sequence, named Pas2r12, consisting of a repeated Pas sequence (FFLIG-FFLIG) and d-dodeca-arginine (r12). This peptide significantly enhanced the cellular uptake and cytosolic release of enhanced green fluorescent protein and immunoglobulin G as cargos. We found that simply mixing Pas2r12 with cargos could generate cytosolic introducible forms. The cytosolic delivery of cargos by Pas2r12 was found to be an energy-requiring process, to rely on actin polymerization, and to be suppressed by caveolae-mediated endocytosis inhibitors (genistein and methyl-ß-cyclodextrin) and small interfering RNA against caveolin-1. These results suggest that Pas2r12 enhances membrane penetration of cargos without the need for cross-linking and that caveolae-mediated endocytosis may be the route by which cytosolic delivery is enhanced.

Suppression of cell cycle progression by poly(ADP-ribose) polymerase inhibitor PJ34 in neural stem/progenitor cells.

Neural stem/progenitor cells (NSPCs) express higher levels of poly(ADP-ribose) polymerase 1 (PARP1) than mouse embryonic fibroblasts (MEFs). Inhibition of PARP induces the expression of several genes in the p53 signaling pathway, including p21, which is critical for cell cycle control at the G1/S phase, triggers apoptosis, and suppresses cell cycle progression in NSPCs. However, upon the up-regulation of p21, the cell cycle does not arrest at any specific phase. In the present study, the expression of genes specific to the G1/S and G2/M phases of the cell cycle were analyzed following treatment with PJ34 (N-[6-oxo-5,6-dihydro-phenanthridin-2-yl]-N,N-dimethylacetamide), an inhibitor of PARP. PJ34 treatment dramatically down-regulated cyclin B1 expression in NSPCs, but not in MEFs, which was confirmed by a promoter assay. Down-regulation of FoxM1 and B-MYB revealed that the down-regulation of cyclin B occurs at the transcriptional level. GADD45 was also specifically up-regulated in NSPCs. Taken together, the activation of p53 by PJ34 treatment in NSPCs induced changes in the expression of genes involved in the cell cycle. Fluorescence-activated cell sorting analysis revealed that PJ34 treatment suppressed G2/M to G1 progression in NSPCs, but not in MEFs. These data indicate that PJ34 treatment inhibits cyclin expression at the mRNA level and suppresses cell cycle progression in NSPCs.

A case of laparoscopy-assisted vaginal cuff suturing for vaginal cuff dehiscence after total laparoscopic hysterectomy.

INTRODUCTION: Vaginal cuff dehiscence after hysterectomy is a rare complication and occurs in less than 1% of patients. It can present with serious complications, such as bowel evisceration and peritonitis. PRESENTATION OF CASE: A 51-year-old multigravida Korean woman underwent total laparoscopic hysterectomy for leiomyoma. Six months later, she reported lower abdominal pain and vaginal bleeding. Physical examination revealed rebound tenderness in the lower abdomen, and pelvic examination showed a small amount of vaginal bleeding with an evisceration of the small intestine through the vagina that exhibited healthy peristalsis. The eviscerated bowel, which seemed to be a part of the ileum, was carefully manually reduced transvaginally into the abdominal cavity. Laparoscopic observation revealed adhesions between the omentum, small intestine, and the peritoneum. Specifically, the small intestine was adhered around the vaginal cuff. An abdominal abscess was found in the left lower abdominal cavity. An adhesiotomy was performed and the abdominal abscess was removed and irrigated. Complete separation of the anterior and posterior vaginal cuff edges was obtained. The vaginal cuff was closed with interrupted 0-polydioxanone absorbable sutures without bowel injury. A 6-month follow-up examination revealed complete healing of the vaginal cuff. DISCUSSION: In this case, we were able to make use of both laparoscopic and transvaginal methods to perform a successful repair with a minimally invasive and safe technique. CONCLUSION: Laparoscopically assisted vaginal cuff suturing for vaginal cuff dehiscence after total laparoscopic hysterectomy was found to be effective, safe, and minimally invasive.

Poly(ADP-ribose) polymerase inhibitors activate the p53 signaling pathway in neural stem/progenitor cells.

BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1), which catalyzes poly(ADP-ribosyl)ation of proteins by using NAD+ as a substrate, plays a key role in several nuclear events, including DNA repair, replication, and transcription. Recently, PARP-1 was reported to participate in the somatic cell reprogramming process. Previously, we revealed a role for PARP-1 in the induction of neural apoptosis in a cellular model of cerebral ischemia and suggested the possible use of PARP inhibitors as a new therapeutic intervention. In the present study, we examined the effects of PARP inhibitors on neural stem/progenitor cells (NSPCs) of the mouse brain. RESULTS: PARP-1 was more abundant and demonstrated higher activity in NSPCs than in mouse embryonic fibroblasts. Treatment with PARP inhibitors suppressed the formation of neurospheres by NSPCs through the suppression of cell cycle progression and the induction of apoptosis. In order to identify the genes responsible for these effects, we investigated gene expression profiles by microarray analyses and found that several genes in the p53 signaling pathway were upregulated, including Cdkn1a, which is critical for cell cycle control, and Fas, Pidd, Pmaip1, and Bbc3, which are principal factors in the apoptosis pathway. Inhibition of poly(ADP-ribosyl)ation increased the levels of p53 protein, but not p53 mRNA, and enhanced the phosphorylation of p53 at Ser18. Experiments with specific inhibitors and also shRNA demonstrated that PARP-1, but not PARP-2, has a role in the regulation of p53. The effects of PARP inhibitors on NSPCs were not observed in Trp53 -/- NSPCs, suggesting a key role for p53 in these events. CONCLUSIONS: On the basis of the finding that PARP inhibitors facilitated the p53 signaling pathway, we propose that poly(ADP-ribosyl)ation contributes to the proliferation and self-renewal of NSPCs through the suppression of p53 activation.

Assessment of drug content uniformity of atropine sulfate triturate by liquid chromatography-tandem mass spectrometry, X-ray powder diffraction, and Raman chemical imaging.

BACKGROUND: Atropine sulfate is an anticholinergic agent for treatment of hypertrophic pyloric stenosis and is orally administrated as a triturate with lactose hydrate. Because of the low safety margin of atropine sulfate, triturate uniformity is a key safety factor. In this study, we assessed the uniformity of atropine sulfate in 1000-fold triturates prepared by wet mixing and dry mixing methods and discussed the cause of the difference in uniformity between two preparation methods. METHODS: A 1000-fold triturate of atropine sulfate with lactose hydrate was prepared by two different methods: wet mixing and dry mixing. The wet mixing was performed according to Kurashiki Central Hospital protocol and the dry mixing was a simple physical mixing by a rocking mixer. The uniformity of atropine sulfate content in aliquots of a 1000-fold triturate with lactate hydrate was assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification. Solid-state analyses of the triturates by Raman chemical imaging and X-ray powder diffraction (XRPD) were performed to investigate the difference in uniformity. RESULTS: The LC-MS/MS quantification showed that the uniformity of atropine sulfate in the 1000-fold triturate was excellent for wet mixing but was significantly variable for dry mixing. On the basis of the Raman chemical imaging and XRPD analyses, it was indicated that an amorphous thin film of atropine sulfate coated the surfaces of the lactose hydrate particles during wet mixing and contributed to the uniformity of the triturate. In contrast, clusters of the crystalline atropine sulfate were found in the dry mixing samples. CONCLUSION: The results showed that better atropine sulfate triturate uniformity was achieved using the wet mixing method rather than the dry method and the cause of the uniformity difference between two mixing methods was indicated by the multilateral assessment.

Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder.

AIMS: The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode. METHODS: A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables. RESULTS: Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI. CONCLUSION: Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.

Translin-associated factor X gene (TSNAX) may be associated with female major depressive disorder in the Japanese population.

Several investigations have reported that the translin-associated factor X gene (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) was associated with major psychiatric disorders including schizophrenia, bipolar disorder (BP), and major depressive disorder (MDD). TSNAX is located immediately upstream of DISC1, and has been shown to undergo intergenic splicing with DISC1. It thus may also be influenced by translocation. To our knowledge, there are no reported gene-based association analyses between TSNAX and mood disorders in the Japanese population. We conducted a case-control study of Japanese samples (158 bipolar patients, 314 major depressive disorder patients, and 811 controls) with three tagging SNPs in TSNAX, selected using HapMap database. In addition, we performed an association analysis between TSNAX and the efficacy of fluvoxamine treatment in 120 Japanese patients with MDD. The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. We found an association between rs766288 in TSNAX and female MDD in the allele/genotype analysis. However, we did not find any association between TSNAX and BP or the fluvoxamine therapeutic response in MDD in the allele/genotype analysis or haplotype analysis. Our results suggest that rs766288 in TSNAX may play a role in the pathophysiology of female MDD in the Japanese population. A replication study using larger samples may be required for conclusive results, since our sample size was small.

Retrospective serological tests for determining the optimal blood concentration of voriconazole for treating fungal infection.

We investigated the optimal blood concentration of voriconazole (VRCZ) based on trough blood concentrations (C) and serological test values in patients. With regard to the regulation of VRCZ dosage (D) to maintain optimal blood concentrations, we investigated the relationship between C and D. Twenty-three patients were enrolled in the present study, and at 28 point data were analyzed retrospectively.When the beta-D-glucan or the Aspergillus antigen were decreased below the standard set values, it was evaluated as effective. The adverse events were evaluated using the Common Terminology Criteria for Adverse Events ver. 3.0. We found a significant difference (p<0.05) in the average trough blood concentration between patients in whom VRCZ was effective and those in whom VRCZ was ineffective (8.21+/-2.19 microg/ml vs. 1.01+/-0.86 microg/ml), and patients presenting with adverse events and those with no adverse events (7.64+/-2.84 microg/ml vs. 1.49+/-1.79 microg/ml). There was no significant relationship between C and D (C: D, y=0.018-2.186, r(2)=0.349).Improved efficacy and more adverse events thus occurred with higher blood concentrations. The careful regulation of the dosage must be performed while measuring blood concentration and observing for adverse events. The implementation of therapeutic drug monitoring for VRCZ is a valuable tool for achieving effective fungal infection therapy and should be aggressively investigated in future studies.

Terpenoids and a diarylheptanoid from Zingiber ottensii.

Four new terpenoids and a diarylheptanoid were isolated together with 16 known compounds from rhizomes of Zingiber ottensii. The structures of the new compounds were determined to be 1,10,10-trimethylbicyclo[7,4,0]tridecane-3,6-dione (1), (E)-14-hydroxy-15-norlabda-8(17),12-dien-16-al (2), (E)-labda-8(17),12,14-trien-15(16)-olide (3), (E)-14,15,16-trinorlabda-8(17),11-dien-13-oic acid (4), and rel-(3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3, 4-dihydroxyphenyl)heptane (5) by spectroscopic evidence.