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A 49-year-old female patient was transferred to our hospital due to suspicion of severe adhesion and malignant tumours during surgery at a local hospital with an adnexal tumour a week ago. There was no history of gynaecological surgery before this surgery. On pelvic examination, a solid, fixed mass

Background/aim Non-invasive biomarker detection using DNA from cell-free circulating DNA (cfDNA) and circulating tumor cells (ctcDNA) are emerging as they can be used for early diagnosis, prognosis and therapeutic target selection for cancer. However, cfDNA and ctcDNA from the same patient have not yet been compared extensively on how different the genetic characteristics of the two are in terms of the overlap between them. Materials and methods The performance of a customized NGS panel was used to compare the variants found in the 20 pairs of cfDNA and ctcDNA from gynecological cancer patients. Results A genetic variant analysis revealed that there were only nine common overlapping variants out of 63 between the cfDNA and ctcDNA pairs, while 31 and 22 were unique to cfDNA and ctcDNA, respectively. Conclusion A combinatory analysis of both cfDNA and CTCs from cancer patients can improve the sensitivity of liquid biopsies. These results are expected to provide better genetic target information for guiding clinical strategies for cancer.

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic&ndash, pituitary&ndash, gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the &alpha, amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.

Introduction: Hepatoid carcinoma of the ovary (HCO) is a rare disease that originates from the ovarian surface epithelium. It is histologically characterized as hepatocellular carcinoma (HCC) with a hepatocyte-rich granular cytoplasm. Patient concerns: A 65-year-old female patient was admitted with complaints of indigestion, abdominal bloating, and pain. Diagnosis: The patient showed an elevated level of serum alpha-fetoprotein (AFP) with abdominal bloating and pain. After surgery and histopathology analysis, she was finally diagnosed with HCO, Figo stage IC. Interventions: After cytoreductive surgery, she underwent adjuvant chemotherapy with carboplatin and paclitaxel. Although the disease was diagnosed at an early stage, it recurred 6 months after completion of adjuvant chemotherapy. Elevation of serum AFP level and removal of a mass from the lumbar vertebra confirmed the recurrence of this disease. Subsequently, the patient underwent radiation therapy and palliative chemotherapy. Outcomes: She died 31 months after the diagnosis due to disease progression. Conclusion: The aggressive nature of HCO was clearly observed in this case despite early diagnosis and treatment. Further studies are needed to understand the proper treatment and prognostic factors of HCO.

Lamina II, also called the substantia gelatinosa (SG) of the medullary dorsal horn (the trigeminal subnucleus caudalis, Vc), is thought to play an essential role in the control of orofacial nociception because it receives the nociceptive signals from primary afferents, including thin myelinated Aδ- and unmyelinated C-fibers. Glycine, the main inhibitory neurotransmitter in the central nervous system, plays an essential role in the transference of nociceptive messages from the periphery to higher brain regions. Bisphenol A (BPA) is reported to alter the morphological and functional characteristics of neuronal cells and to be an effector of a great number of ion channels in the central nervous system. However, the electrophysiological effects of BPA on the glycine receptors of SG neurons in the Vc have not been well studied. Therefore, in this study, we used the whole-cell patch-clamp technique to determine the effect of BPA on the glycine response in SG neurons of the Vc in male mice. We demonstrated that in early neonatal mice (0-3 postnatal day mice), BPA did not affect the glycine-induced inward current. However, in the juvenile and adult groups, BPA enhanced the glycine-mediated responses. Heteromeric glycine receptors were involved in the modulation by BPA. The interaction between BPA and glycine appears to have a significant role in regulating transmission in the nociceptive pathway.

Cavernous hemangiomas rarely involve the female genital tract. It is difficult to identify vascular malformations when these lesions are concealed in the vagina or deep vulva area. We present a rare case of vaginal cavernous hemangioma in a 30-year-old primiparous woman with an early severe postpartum hemorrhage (PPH) and delayed continuous bleeding from the episiotomy site. She was treated successfully with transarterial embolization of the left vaginal artery. To our knowledge, this is the first reported case of PPH caused by rupture of a vaginal hemangioma during vaginal delivery in English literature.

The survival of patients with recurrent cervical cancer following irradiation remains poor. Chemotherapy combined with hyperthermia has been demonstrated to improve the response rate. The present study was performed to evaluate the effect of modulated electro-hyperthermia combined with conventional chemotherapy compared with chemotherapy alone on recurrent cervical cancer previously treated with irradiation. A total of 20 patients were treated with chemotherapy alone, and 18 were treated with chemotherapy combined with modulated electro-hyperthermia. A single patient was treated with chemo-radiotherapy as primary treatment and then relapsed; the tumor was inoperable and radio-refractory upon recurrence. Local metastases, including metastasis of the para-aortic lymph nodes and adjacent pelvic lymph nodes were included, but distant metastases were excluded. Modulated electro-hyperthermia was performed three times per week beginning at chemotherapy initiation, and patients underwent a total of 36 sessions. The overall response (complete remission + partial remission + stable disease/progressive disease) to treatment was significantly greater in the group of patients who underwent chemotherapy combined with modulated electro-hyperthermia (P=0.0461), and at the evaluation conducted at the last follow-up visit, the response rate was significantly higher (P=0.0218). Additionally, severe complications were not reported. In the present study, of patients with recurrent cervical cancer previously treated with irradiation, the overall response rate for patients treated with chemotherapy combined with modulated electro-hyperthermia was significantly greater than that for those treated with chemotherapy alone.

Background Early diagnosis and continuous monitoring are necessary for an efficient management of cervical cancers (CC). Liquid biopsy, such as detecting circulating tumor DNA (ctDNA) from blood, is a simple, non-invasive method for testing and monitoring cancer markers. However, tumor-specific alterations in ctDNA have not been extensively investigated or compared to other circulating biomarkers in the diagnosis and monitoring of the CC. Therfore, Next-generation sequencing (NGS) analysis with blood samples can be a new approach for highly accurate diagnosis and monitoring of the CC. Method Using a bioinformatics approach, we designed a panel of 24 genes associated with CC to detect and characterize patterns of somatic single-nucleotide variations, indels, and copy number variations. Our NGS CC panel covers most of the genes in The Cancer Genome Atlas (TCGA) as well as additional cancer driver and tumor suppressor genes. We profiled the variants in ctDNA from 24 CC patients who were being treated with systemic chemotherapy and local radiotherapy at the Jeonbuk National University Hospital, Korea. Result Eighteen out of 24 genes in our NGS CC panel had mutations across the 24 CC patients, including somatic alterations of mutated genes (ZFHX3–83%, KMT2C-79%, KMT2D-79%, NSD1–67%, ATM-38% and RNF213–27%). We demonstrated that the RNF213 mutation could be used potentially used as a monitoring marker for response to chemo- and radiotherapy. Conclusion We developed our NGS CC panel and demostrated that our NGS panel can be useful for the diagnosis and monitoring of the CC, since the panel detected the common somatic variations in CC patients and we observed how these genetic variations change according to the treatment pattern of the patient.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is admitted as a pivotal site of integrating and regulating orofacial nociceptive inputs. Although citral (3,7-dimethyl-2,6-octadienal) is involved in antinociception, the action mechanism of citral on the SG neurons of the Vc has not been fully clarified yet. In this study, we examined the direct membrane effects of citral and how citral mediates responses on the SG neurons of the Vc in juvenile mice using a whole-cell patch-clamp technique. Under high chloride pipette solution, citral showed repeatable inward currents that persisted in the presence of tetrodotoxin, a voltage-gated Na+ channel blocker, and 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, D-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. However, the citral-induced inward currents were partially blocked by picrotoxin, a gamma-aminobutyric acid (GABAA)-receptor antagonist, or by strychnine, a glycine receptor antagonist. Further, the citral-induced responses were almost blocked by picrotoxin with strychnine. We also found that citral exhibited additive effect with GABA-induced inward currents and glycine-induced inward currents were potentiated by citral. In addition, citral suppressed the firing activities by positive current injection on the SG neurons of the Vc. Taken together, these results demonstrate that citral has glycine- and/or GABA-mimetic actions and suggest that citral might be a potential target for orofacial pain modulation by the activation of inhibitory neurotransmission in the SG area of the Vc.

Background Ovarian mature cystic teratomas comprise tissues derived from all three germ layers. In rare incidences, malignant tumors may arise from ovarian mature cystic teratoma, which occurs in 0.2–1.8% of cases. A variety of tumors can arise within mature cystic teratoma, among which malignant melanoma is exceedingly rare. Case presentation A 42-year-old woman presented with abdominal pain. Transvaginal ultrasonography showed mixed echogenic cystic masses in both ovaries. Her serum cancer antigen (CA19–9) level was elevated at 29,770 U/ml. Surgical excision was performed. Histologic examination showed infiltrating nests of pleomorphic cells with prominent nucleoli and black pigments in the background of a mature cystic teratoma. These pleomorphic cells showed strong immunoreactivity for Melan-A and HMB-45. The patient was re-evaluated and the possibility of a melanoma at any other site was ruled out. Based on these findings, we concluded that the malignant melanoma originated from the ovarian mature cystic teratoma. Conclusion We report a rare case of primary malignant melanoma derived from an ovarian mature cystic teratoma.

The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. One of the key research fields involves the separation and detection of circulating tumor cells (CTC) because of their suggested important role in early cancer diagnosis and prognosis, namely, providing easy access by a liquid biopsy from blood to identify metastatic cells before clinically detectable metastasis occurs and to study the molecular and genetic profile of these metastatic cells. Provided the opportunity to further progress the development of technology for treating cancer, several CTC technologies have been proposed in recent years by various research groups and companies. Despite their potential role in cancer healthcare, CTC methods are currently mainly used for research purposes, and only a few methods have been accepted for clinical application because of the difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack of thorough clinical validation. Therefore, the standardization and clinical application of various developed CTC technologies remain important subsequent necessary steps. Because of their suggested future clinical benefits, we focus on describing technologies using whole blood samples without any pretreatment and discuss their advantages, use, and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based, and density-based methods or combinations of these methods as well as positive and negative enrichment during separation. Although current CTC technologies have not been truly implemented yet, they possess high potential as future clinical diagnostic techniques for the individualized therapy of patients with cancer. Thus, a detailed discussion of the clinical suitability of these new advanced technologies could help prepare clinicians for the future and can be a foundation for technologies that would be used to eliminate CTCs in vivo.

A 70-year-old multiparous woman was diagnosed with an ovarian tumour at a local obstetrics and gynaecology clinic with abdominal pain that started 2 weeks prior and was transferred to our hospital. A movable mass as large as the woman’s fist was palpated in the right adnexa on pelvic examination

SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-β1, and smad2/3, and decreasing the expression of E-cadherin, the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.

Paraneoplastic autoimmune multiorgan syndrome (PAMS), also known as paraneoplasic pemphigus, involves the skin, internal organs and mucosa. PAMS-associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize PAMS. The most common symptoms of PAMS include pain associated with continuous oral ulceration and resistance to pharmacological treatment. The present study reports the case of a 42-year-old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region, oral mucosa and vaginal mucosa. The patient was diagnosed with PAMS based on computed tomography scans and histological analyses of the lesions. The lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia. However, the oral lesion was treated with intraluminal brachytherapy due to its resistance to long-term pharmacological treatment. The majority of the lesions were improved following treatment, in the absence of any severe side effects. In addition, neither worsening nor progression of the oral lesion was observed during the 4-year follow-up period.

Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 μM tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 μM strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with α₂/α₂β subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically.

A 34-year-old woman was admitted to the hospital with lower abdominal discomfort for several months. Her menstrual cycle length was 28 days, and she experienced slight menstrual pain. A soft, movable mass was palpated in the right adnexal region of the uterus on pelvic examination. Her routine

A 55-year-old woman presented to the hospital with abdominal discomfort over 3 months. Contrast-enhanced abdominal CT showed a 10×9×6.5 cm sized well-defined solid-cystic enhancing mass in the right pelvic cavity. Under general anaesthesia, exploratory laparotomy was performed on suspicion of ovarian malignancy. Pathological examination revealed a retroperitoneal schwannoma with highly ordered cellular component (Antoni A) and hypocellularity with predominantly loose myxoid component (Antoni B). On immunohistochemical staining, the sample showed typically positive result for S-100 in the cytoplasm of the tumour cells. Schwannomas are consisting only of Schwann cells and are most often non-malignant tumors. It is relatively slow growing and usually located in the head, neck and the extremities. Schwannomas are quite rare in the retroperitoneal region. The diagnosis of retroperitoneal schwannomas is often delayed and misdiagnosed as an adnexal tumour, especially locating in the pelvic cavity. Surgical complete resection of tumour is the treatment of choice and recurrence is unusual after complete resection.

A 50-year-old woman was admitted to our hospital with a 2-day history of cramping pain of the lower abdomen. She also reported an episode of nausea and vomiting prior to admission. The patient had undergone total abdominal hysterectomy for uterine myoma. Her blood pressure was 100/60 mm Hg, pulse rate of 70 beats/min and axillary temperature of 36.5°C. The patient had mild direct tenderness of the lower abdomen, especially at the right lower quadrant, with no rebound tenderness or muscular guarding. Laboratory data showed a white cell count of 10 100/mm3 (normal limit of 4000–10 000/mm3) and a C reactive protein concentration of 17.25 mg/L (normal limit of 0–10 mg/L). A plain chest X-ray revealed no free air under diaphragm. Pelvic ultrasound demonstrated smooth bilocular cystic tumour within the right adnexa that has no …

A 16-year-old female with Ewing sarcoma, a very rare disease with poor prognosis in women, was admitted to the hospital with abdominal pain. Diagnostic laparotomy revealed the Ewing sarcoma originating from the extramural uterus. Histological examination yielded positive test results for CD99, vimentin, S-100, eosin 5-maleimide and periodic acid-Shiff. EWS-FLI1 type 1 translocation was confirmed. Fibroblast growth factor receptor (FGFR) 4 (c.1162G> A) and HRas proto-oncogene (HRAS; c.182A> G) mutations were also detected. At eight months following complete remission, pelvic lymph node metastasis was confirmed. Epithelial cell adhesion molecule-positive circulating tumor cells (CTCs) were detected in liquid biopsy. FGFR3 (c.1948A> G) and FGFR4 (c.1162G> A) mutations were found in the CTCs. FGFR4 (c.1162G> A) and HRAS (c.182A> G) mutations were confirmed in cell-free circulating tumor DNA. A sequence of EWSR1 gene was also confirmed in the CTCs. To the best of our knowledge, this is the first report of skeletal Ewing sarcoma being detected using multiple noninvasive diagnostic methods to observe genetic translocation and mutation in blood CTCs. It may be used to monitor the therapeutic effect of cancer or predict prognosis. Therefore, liquid biopsy is expected to serve a pivotal role in ultra-precise medicine in the future.

Mild hyperthermia has been known to enhance the response of tumours to radiotherapy or chemotherapy by increasing tumour blood flow, thereby increasing tumour oxygenation or drug delivery. The purpose of this study was to assess the changes in temperature and blood flow in human cervical cancer in response to regional heating with modulated electro-hyperthermia (mEHT).The pelvic area of 20 patients with cervical carcinoma was heated with mEHT. The peri-tumour temperature was measured using an internal organ temperature probe. The tumour blood flow was measured using 3D colour Doppler ultrasound by determining the peak systolic velocity/end-diastolic velocity ratio (S/D ratio) and the resistance index (RI) within blood vessels.The mean peri-tumour temperature was 36.7 ± 0.2 °C before heating and increased to 38.5 ± 0.8 °C at the end of heating for 60 min. The marked declines in RI and S/D values strongly demonstrated that heating significantly increased tumour blood perfusion.Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.

Taurine is an essential amino-sulfonic acid having a fundamental function in the brain, participating in both cell volume regulation and neurotransmission. Using a whole cell voltage patch clamp technique, the taurine-activated neurotransmitter receptors in the preoptic hypothalamic area (PHA) neurons were investigated. In the first set of experiments, different concentrations of taurine were applied on PHA neurons. Taurine-induced responses were concentration-dependent. Taurine-induced currents were action potential-independent and sensitive to strychnine, suggesting the involvement of glycine receptors. In addition, taurine activated not only α-homomeric, but also αβ-heteromeric glycine receptors in PHA neurons. Interestingly, a low concentration of taurine (0.5mM) activated glycine receptors, whereas a higher concentration (3mM) activated both glycine and gamma-aminobutyric acid A (GABAA) receptors in PHA neurons. These results suggest that PHA neurons are influenced by taurine and respond via glycine and GABAA receptors.

Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus. Notably, auranofin treatment in SKOV3 cells also resulted in the downregulation of the expression levels of both Her2 and phosphorylated Akt. Thus, Her2 was identified as the common molecular target protein by siRNA transfection against MUC4. Western blot analysis of total and nuclear fraction lysates from SKOV3 cells revealed that attenuation of MUC4 combined with auranofin treatment in SKOV3 cells synergistically activated FOXO3 translocation from the cytoplasm to the nucleus through the regulation of the Her2/Akt/FOXO3 pathway. Attenuation of MUC4 by siRNA transfection potentiated the antitumor effect of auranofin which was examined by performing in vitro assays such as WST-1, cell counting, colony formation, TUNEL and Annexin V staining. In addition, western blot analysis of the apoptosis‑related proteins such as PARP1, caspase-3, Bim extra large (EL), Bax and Bcl2 revealed that the attenuation of MUC4 by siRNA transfection potentiates the pro-apoptotic activity of auranofin in SKOV3 cells. Collectively, auranofin could regulate the Her2/Akt/FOXO3 signaling pathway in SKOV3 cells and be used as a potential antitumor agent considering the expression of MUC4 in ovarian cancer patients.

RATIONALE Wolf-Hirschhorn Syndrome (WHS) is a rare disorder caused by the loss of the distal part of the short arm of chromosome 4, and has various phenotypes depending on the deletion size. Although many articles report on urinary tract malformations or ophthalmologic abnormalities, there are few descriptions of the skeletal anomalies. This is an extremely rare case of cervical dysplasia in WHS. PATIENT CONCERNS A 24-year-old pregnant woman was transferred to our hospital at 21 gestational weeks for intrauterine growth retardation and oligohydramnios and decided to preserve the pregnancy after evaluation. A female was born at full term by normal vaginal delivery, weighing 1791 g. The patient was suspected to have congenital dysplasia of the cervical vertebrae on the routine newborn chest radiograph, and cervical spine magnetic resonance imaging revealed nonossification of the C3 and C4 vertebral bodies. DIAGNOSIS The newborn had the "Greek warrior helmet" face typical of WHS. A deletion was detected in the distal portion of the short arm of chromosome 4 (p 16.3) by fluorescence in situ hybridization analysis. INTERVENTIONS She was hospitalized for nutritional management and congenital anomaly evaluation for a month before being discharged with rehabilitation and antiepileptic drugs. OUTCOMES The patient has been readmitted with seizure attacks 5 times to date. At one year of age, she still shows severe head lag and feeding problems. Her last weight was below the 3rd centile. LESSONS Although cervical dysplasia is a rarely reported morphology in WHS, it may provide artefacts for diagnosing WHS as cervical anomalies, unlike facial anomalies or developmental delays, are seldom found in congenital disease.

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (IGly). Firstly, we examined with a 5-HT1 receptor agonist (8-OH-DPAT, 5-HT1/7 agonist, co-applied with SB-269970, 5-HT7 antagonist) and antagonist (WAY-100635), but 5-HT1 receptor agonist did not increase IGly and in the presence of 5-HT1 antagonist, the potentiation of 5-HT on IGly still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT2 receptor mimicked and inhibited the enhancing effect of 5-HT on IGly in the SG neurons, respectively. We also verified the role of the 5-HT7 receptor by using a 5-HT7 antagonist (SB-269970) but it also did not block the enhancement of 5-HT on IGly. Our study demonstrated that 5-HT facilitated IGly in the SG neurons of the Vc through the 5-HT2 receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

Korean red ginseng (KRG) has been used worldwide as a traditional medicine for the treatment of various reproductive diseases. Gonadotropin releasing hormone (GnRH) neurons are the fundamental regulators of pulsatile release of gonadotropin required for fertility. In this study, an extract of KRG (KRGE) was applied to GnRH neurons to identify the receptors activated by KRGE. The brain slice patch clamp technique in whole cell and perforated patch was used to clarify the effect of KRGE on the membrane currents and membrane potentials of GnRH neurons. Application of KRGE (3 μg/μL) under whole cell patch induced remarkable inward currents (56.17±7.45 pA, n=25) and depolarization (12.91±3.80 mV, n=4) in GnRH neurons under high Cl(-) pipette solution condition. These inward currents were not only reproducible, but also concentration dependent. In addition, inward currents and depolarization induced by KRGE persisted in the presence of the voltage gated Na(+) channel blocker tetrodotoxin (TTX), suggesting that the responses by KRGE were postsynaptic events. Application of KRGE under the gramicidin perforated patch induced depolarization in the presence of TTX suggesting its physiological significance on GnRH response. Further, the KRGE-induced inward currents were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA glutamate receptor antagonist, 10 μM) or picrotoxin (PIC; GABAA receptor antagonist, 50 μM), and almost blocked by PIC and CNQX mixture. Taken together, these results suggest that KRGE contains ingredients with possible GABA and non-NMDA glutamate receptor mimetic activity, and may play an important role in the endocrine function of reproductive physiology, via activation of GABAA and non-NMDA glutamate receptors in GnRH neurons.

Heme oxygenase-1 (HO-1), an inducible enzyme with broad tissue expression, is wel1-regulated in response to hematopoietic stress and preserves vascular homeostasis. We investigated the involvement of HO-1 in HL-60 cell differentiation. Dimethyl sulfoxide (DMSO) completely decreased HO-1 expression in a time-dependent manner, but clearly induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression. Interestingly, zinc protoporphyrin (ZnPP), a strong inhibitor of HO-1, induced HL-60 cell differentiation. In contrast, treatment with cobalt protoporphyrin (CoPP), an activator of HO-1, decreased CD11b expression. Additionally, ZnPP downregulated HO-1 protein expression in HL-60 cells, whereas CoPP induced upregulation. These results suggest that HO-1 might have a negative function in DMSO-induced HL-60 cell differentiation. This study provides the first evidence that HO-1 plays an important role in DMSO-induced HL-60 cell differentiation. [BMB reports 2011; 44(11): 753-757]

Background Recent reports have shown that deleted in breast cancer 1 (DBC1/CCAR2) is an indicator of poor prognosis of various human cancers. However, its expression in ovarian carcinoma has not been reported. Methods We investigated the immunohistochemical expression of DBC1 and BRCA1 and their prognostic significance in 104 ovarian carcinomas. Survival analyses were performed according to the Kaplan-Meier method, as well as univariate and multivariate Cox proportional hazard regression analysis. Results Positive expression of DBC1 and BRCA1 were seen in 63% (66/104) and 44% (46/104) of overall ovarian carcinomas, respectively. DBC1 expression was significantly associated with advanced clinicopathological factors such as high tumor stage, latent distant metastasis, platinum-resistance, elevated serum levels of CA125, high histologic grade, and BRCA1 expression. In the histological subtypes of ovarian carcinomas, DBC1 expression was more common in serous carcinoma (72%, 54/75) than mucinous carcinoma (15%, 3/20). BRCA1 expression was significantly associated with latent distant metastasis, platinum-resistance, and higher histologic grade. In addition, DBC1 expression was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) in 104 ovarian carcinomas (OS; P

Peripheral neuropathy is a frequent complication of diabetes mellitus and a common symptom of neuropathic pain, the mechanism of which is complex and involves both peripheral and central components of the sensory system. The lamina II of the medullary dorsal horn, called the substantia gelatinosa (SG), is well known to be a critical site for processing of orofacial nociceptive information. Although there have been a number of studies done on diabetic neuropathy related to the orofacial region, the action of neurotransmitter receptors on SG neurons in the diabetic state is not yet fully understood. Therefore, we used the whole-cell patch clamp technique to investigate this alteration on SG neurons in both streptozotocin (STZ)-induced diabetic mice and offspring from diabetic female mice. STZ (200 mg/kg)-injected mice showed a small decrease in body weight and a significant increase in blood glucose level when compared with their respective control group. However, application of different concentrations of glycine, gamma-aminobutyric acid (GABA) and glutamate on SG neurons from STZ-injected mice did not induce any significant differences in inward currents when compared to their control counterparts. On the other hand, the offspring of diabetic female mice (induced by multiple injections of STZ (40 mg/kg) for 5 consecutive days) led to a significant decrease in both body weight and blood glucose level compared to the control offspring. Glycine and glutamate responses in the SG neurons of the offspring from diabetic female mice were similar to those of control offspring. However, the GABA response in SG neurons of offspring from diabetic female mice was greater than that of control offspring. Furthermore, the GABA-mediated responses in offspring from diabetic and control mice were examined at different concentrations ranging from 3 to 1,000 μM. At each concentration, the GABA-induced mean inward currents in the SG neurons of offspring from diabetic female mice were larger than those of control mice. These results demonstrate that SG neurons in offspring from diabetic mice are more sensitive to GABA compared to control mice, suggesting that GABA sensitivity may alter orofacial pain processing in offspring from diabetic female mice.

Conventionally, myomectomy during cesarean section is reserved only for pedunculated myomas because resection of myomas at the time of cesarean section usually stimulates profuse bleeding. Thirty-one patients underwent myomectomy using purse-string suture during cesarean section. Myoma could be excised without profuse bleeding, while an assistant maintains strong tension on the purse-string suture around the myoma. The suture was tightened and tied immediately after complete resection of the myoma and then stitches of another purse-string suture were placed alternately with each previous stitch in the inner side of the first suture. We have used this method for more than 3 years and have not observed failures and serious complications, such as late hemorrhage and uterine rupture during a subsequent pregnancy. Myomectomy using purse-string suture during cesarean section is a safe, useful, and convenient technique.

Spontaneous perforation is a very rare complication of pyometra. The clinical findings of perforated pyometra usually mimic perforation of the gastrointestinal tract. In most cases a correct diagnosis can be made only by laparotomy. In our case, the patient's pyometra was sealed and she complained only of mild abdominal pain and showed no signs of peritonitis. Ultrasonography and computed tomography (CT) findings were not suggestive of uterine rupture. However, T2-weighted magnetic resonance imaging (MRI) demonstrated a full thickness defect of the myometrium. We discuss the CT and MRI findings that confirmed a correct diagnosis of perforated pyometra. J. Magn. Reson. Imaging 2010;32:697–699. © 2010 Wiley-Liss, Inc.

The plant Withania somnifera (WS), also known as Ashwagandha, has been used widely in traditional medicine systems in India and Nepal (Ayurveda), and has been accepted to cure various ailments. In this study, the whole-cell patch clamp technique was performed to examine the mechanism of action of WS on the SG neurons of the Vc from mouse brainstem slices. In whole-cell patch clamp mode, methanol extract of Withania somnifera (mWS) induced short-lived and repeatable inward currents in all SG neurons tested (31.3±8.51 pA, n = 7) using a high chloride pipette solution. The mWS-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated Na+channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, AP5, an NMDA receptor antagonist and strychnine, a glycine receptor antagonist. The mWS induced currents were blocked by picrotoxin, a GABAAreceptor antagonist. These results show that mWS has an inhibitory effects on SG neurons of the Vc through GABAAreceptor-mediated activation of chloride ion channels, indicating that mWS contains compounds with sedative effects on the central nervous system. These results also suggest that mWS may be a potential target for modulating orofacial pain processing.