Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol 1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol 1′-hydroxylation, with a Ki value of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50 equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate the in vivo extent of the observed in vitro interactions

Alternative Embryo Transfer on Day 3 or Day 5 for Reducing the Risk of Multiple Gestations

Purpose: This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos. Methods: All zygotes were cocultured with cumulus cells in 10 ¹l of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro. Results: The number of embryos transferred in period II was 2.9 ± 0.6, while that in period I was 3.7 ± 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%). Conclusions: We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations

Small Molecule Modulators of the Circadian Molecular Clock With Implications for Neuropsychiatric Diseases

Circadian rhythms regulate many biological processes and play fundamental roles in behavior, physiology, and metabolism. Such periodicity is critical for homeostasis because disruption or misalignment of the intrinsic rhythms is associated with the onset and progression of various human diseases and often directly leads to pathological states. Since the first identification of mammalian circadian clock genes, numerous genetic and biochemical studies have revealed the molecular basis of these cell-autonomous and self-sustainable rhythms. Specifically, these rhythms are generated by two interlocking transcription/translation feedback loops of clock proteins. As our understanding of these underlying mechanisms and their functional outputs has expanded, strategies have emerged to pharmacologically control the circadian molecular clock. Small molecules that target the molecular clock may present novel therapeutic strategies to treat chronic circadian rhythm-related diseases. These pharmaceutical approaches may include the development of new drugs to treat circadian clock-related disorders or combinational use with existing therapeutic strategies to improve efficacy via intrinsic clock-dependent mechanisms. Importantly, circadian rhythm disruptions correlate with, and often precede, many symptoms of various neuropsychiatric disorders such as sleep disorders, affective disorders, addiction-related disorders, and neurodegeneration. In this mini-review, we focus on recent discoveries of small molecules that pharmacologically modulate the core components of the circadian clock and their potential as preventive and/or therapeutic strategies for circadian clock-related neuropsychiatric diseases

Primary Culture of Central Neurocytoma: A Case Report

A seventeen-year-old female patient was admitted with sudden-onset of headache and vomiting. Brain magnetic resonance imaging demonstrated a heterogeneously enhancing tumour in the left lateral ventricle. The tumour was removed and confirmed as a central neurocytoma (CN). For the residual tumour in the left lateral ventricle, gamma knife stereotactic radiosurgery was done at fifteen months after the initial surgery. Tumour recurred in the 4th ventricle at 5 yr after initial surgery. The tumour was removed and proved as a CN. In vitro primary culture was done with both tumours obtained from the left lateral ventricle and the 4th ventricle, respectively. Nestin, a neuronal stem cell marker was expressed in reverse Transcriptase-Polymerase Chain Reaction of both tumors. Both tumours showed different morphology and phenotypes of neuron and glia depending on the culture condition. When cultured in insulin, transferrin selenium and fibronectin media with basic fibroblast growth factors, tumour cells showed neuronal morphology and phenotypes. When cultured in the Dulbeco's Modified Essential Media with 20% fetal bovine serum, tumors cells showed glial morphology and phenotypes. It is suggested that CN has the characteristics of neuronal stem cells and potential to differentiate into mature neuron and glial cells depending on the environmental cue

Rapidly Aggravated Dissecting Flap by Angiography during Percutaneous Stent Placement for Acute Isolated Superior Mesenteric Artery Dissection

Acutely aggravated dissecting flap and consequent occlusion of the superior mesenteric artery (SMA) by simple contrast passage during initial angiography for percutaneous stent placement is a uncommon event, which usually is not reported. After analysis of many factors that underlie development of such complications, we present herein one case of successful treatment of isolated SMA dissection and its complications with favorable outcomes during 25 months follow-up after percutaneous stent placement

A Case of a Subepidermal Calcified Nodule on the Sole without Trauma

Subepidermal calcified nodule is an uncommon form of calcinosis cutis, which most commonly occurs in children. It usually presents as an asymptomatic, solitary verrucous nodule on the head and neck region, but occasionally as multiple lesions. Serum calcium and phosphorus levels are usually normal. Histopathology shows well-formed homogeneous eosinophilic material and granules in the upper dermis. Material in the dermis stained with von Kossa was positive. We report on an unusual case of a subepidermal calcified nodule occurring on the sole. A 21-month-old male presented with an oval-shaped, whitish, hard nodule measuring 5×5 mm on the left sole, without any previous history of trauma

Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

<p>Abstract</p> <p>Backgrounds</p> <p>We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment.</p> <p>Methods</p> <p>Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions.</p> <p>Results</p> <p>Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia.</p> <p>Conclusions</p> <p>Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.</p