A novel mutation of ABCC8 gene in a patient with diazoxide-unresponsive congenital hyperinsulinism / 소아과

Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively. We report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth, because of hypoglycemia. Investigations revealed hypoglycemia with hyperinsulinemia, but no ketone bodies, and a low level of free fatty acids. High dose glucose infusion, enteral feeding, and medications could not maintain the patient's serum glucose level. Genetic testing revealed a new variation of ABCC8 mutation. Therefore, we report this case of CHI caused by a novel mutation of ABCC8 in a half-Korean newborn infant with diazoxide-unresponsive hyperinsulinemic hypoglycemia.

Effects of hydrogen peroxide on voltage-dependent K+ currents in human cardiac fibroblasts through protein kinase pathways

Human cardiac fibroblasts (HCFs) have various voltage-dependent K+ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide (H2O2) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether H2O2 could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of H2O2 stimulated Ca2+-activated K+ (K(Ca)) currents but not delayed rectifier K+ or transient outward K+ currents, all of which are VDKCs. H2O2-stimulated K(Ca) currents were blocked by iberiotoxin (IbTX, a large conductance K(Ca) blocker). The H2O2-stimulating effect on large-conductance K(Ca) (BK(Ca)) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated BK(Ca) currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the H2O2-stimulating effect on BK(Ca) currents. Using RT-PCR and western blot analysis, three subtypes of K(Ca) channels were detected in HCFs: BK(Ca) channels, small-conductance K(Ca) (SK(Ca)) channels, and intermediate-conductance K(Ca) (IK(Ca)) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to H2O2, but IbTX decreased H2O2-induced apoptosis. These data suggest that among the VDKCs of HCFs, H2O2 only enhances BK(Ca) currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through BK(Ca) channels.

Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1x10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.

Denys-Drash syndrome, Septated Vagina And Low Level Of Anti-mullerian Hormone In male neonate

There is a wide variety of genital abnormalities observed in patients with Denys-Drash syndrome (DDS). WT1 is thought to influence the genes related to genital development and mutations in this gene have been associated with DDS. DDS should be considered in the differential diagnosis of newborns with genital anomalies. In contrast to other conditions with 46,XY disorders of sex development, individuals with DDS often have duplicated genital organs (a double vagina, cervix or uterus). A double uterus has not yet been reported with 1390G>A (Arg464 Asn) mutation. However, duplicated genitals have been reported with other genetic mutations in patients with DDS. The duplicated genitals in DDS may be associated with low anti-Mullerian hormone (AMH) secretion. Measurement of the AMH levels may add to our understanding of variations in genital development and their abnormalities in disorders such as DDS. In conclusion, this is first case of low level of AMH and double uterus in 1390G>A (Arg464 Asn) mutations of DDS male.

Treatment of Bladder Dysfunction Using Stem Cell or Tissue Engineering Technique

Tissue engineering and stem cell transplantation are two important options that may help overcome limitations in the current treatment strategy for bladder dysfunction. Stem cell therapy holds great promise for treating pathophysiology, as well as for urological tissue engineering and regeneration. To date, stem cell therapy in urology has mainly focused on oncology and erectile dysfunction. The therapeutic potency of stem cells (SCs) was originally thought to derive from their ability to differentiate into various cell types including smooth muscle. The main mechanisms of SCs in reconstituting or restoring bladder function are migration, differentiation, and paracrine effects. Nowadays, paracrine effects of stem cells are thought to be more prominent because of their stimulating effects on stem cells and adjacent cells. Studies of stem cell therapy for bladder dysfunction have been limited to experimental models and have been less focused on tissue engineering for bladder regeneration. Bladder outlet obstruction is a representative model. Adipose-derived stem cells, bone marrow stem cells (BMSCs), and skeletal muscle-derived stem cells or muscle precursor cells are used for transplantation to treat bladder dysfunction. The aim of this study is to review stem cell therapy and updated tissue regeneration as treatments for bladder dysfunction and to provide the current status of stem cell therapy and tissue engineering for bladder dysfunction including its mechanisms and limitations.

Clinical Significance of Antibodies Against Platelet HLA Class I in Children with Idiopathic Thrombocytopenic Purpura / 대한수혈학회지

BACKGROUND: A previous history of transfusion has been known to be associated with production of anti-HLA class I antibodies. However, platelet glycoproteins are the main target of idiopathic thrombocytopenic purpura (ITP). The mechanism of antibody production is known to differ significantly between glycoproteins and anti-HLA class I. The aim of this study was to evaluate the clinical significance of anti-HLA class I antibodies in childhood ITP. METHODS: Enrollment for the normal control group targeted 48 people who visited Gyeongsang National University Hospital from 1990 to 2010, and 48 young children with ITP. Anti-glycoproteins and anti-HLA class I antibodies were tested using the Modified Antigen Capture Enzyme-linked immunosorbent assay (MACE) kit. RESULTS: The positive rate of anti-HLA antibodies was significantly different [36/39 (92.3%) vs 29/46 (63%)] [ITP group vs normal control group] (P=0.002). The mean positive S/C ratio of anti-HLA antibodies was also significantly different (3.55 vs 1.51) [ITP group vs normal control group] (P=0.0000). The positive rate of anti-HLA did not differ significantly between the transfused group and the non-transfused group [12/12 (100%) vs 24/27 (88%)] [transfused ITP vs non-transfused ITP]. The mean positive S/C ratio of anti-HLA antibodies did not differ significantly between the transfused ITP group and the non-transfused ITP group (4.30 vs 3.25) [transfused ITP vs non-transfused ITP]. Consecutive testing showed that positive rate and positive S/C ratio of anti-HLA antibodies did not change significantly between sampling times in both groups [transfused ITP vs non-transfused ITP] (P=1.00 and P=0.15). CONCLUSION: Anti-HLA class I antibodies may be involved in childhood ITP. Transfusion did not affect the course of childhood ITP.

Impact of Nocturia on Abnormal Daytime Sleepiness in Men with Lower Urinary Tract Symptoms/Benign Prostate Hyperplasia / 대한남성과학회지

PURPOSE: Nocturia is one of the most bothersome lower urinary tract symptoms (LUTS). The aim of the present study is to determine whether severe-nocturia have impact on the abnormal daytime sleepiness in men with LUTS/benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Severe-nocturia was classified as twice or more per night. A total of 85 men met the criteria and constituted the study cohort. The patients had a detailed clinical evaluation, including a complete history, physical examination, urine analysis, urine culture, a digital rectal examination, serum prostate-specific antigen (PSA) level, prostate volume by transrectal ultrasonography, uroflowmetry and postvoid residual urine volume. LUTS and symptom-specific quality of life (QoL) were assessed using the IPSS. Patients were asked to complete an Epworth Sleepiness Scale questionnaire for daytime sleepiness. RESULTS: 43 patients had less than one, 42 patients had more than two episodes of nocturia. There was no significant difference of age, total prostate volume, PSA levels between patients with mild-nocturia and severe-nocturia. There was no significant difference of maximum flow rate (Qmax), voided volume and postvoid residual urine volume (PVR) between patients with mild-nocturia and severe-nocturia. There was significant decrease of total International Prostate Symptom Score (IPSS) scores and QoL index in patients with severe-nocturia compared in patients with mild-nocturia. The number of patients with abnormal daytime sleepiness in mild-nocturia and severe-nocturia were 4.7% (2/43), 16.7% (7/42), respectively (p<0.05). Regression coefficiency between percent of nocturia and total score of daytime sleepiness was significant (p<0.05) and regression coefficient (R) was 0.29. CONCLUSIONS: Our results indicate that severe-nocturia had impact on the abnormal daytime sleepiness in patients with LUTS.

Strong Impact of Nocturia on Sleep Quality in Patients with Lower Urinary Tract Symptoms

PURPOSE: Nocturia is a bothersome symptom that impacts sleep quality in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). This study was performed to evaluate the impact of nocturia on sleep quality. MATERIALS AND METHODS: A total of 58 male patients with LUTS/BPH were enrolled. LUTS/BPH patients without nocturia were included in the control group. The inclusion criteria were eight or more points on the International Prostate System Score (IPSS) including more than one episode of nocturia and a prostate volume larger than 20 ml. IPSS, prostate volume, uroflowmetry, and the Pittsburgh Sleep Quality Index (PSQI) from each patient were recorded. RESULTS: Patients with nocturia showed a higher mean global PSQI (8.5+/-0.4) than patients without nocturia (4.82+/-0.4) (p<0.01). Patients with nocturia showed a higher percentage of severe sleep disorders (74.1%) than patients without nocturia (35.3%) (p<0.01). The regression coefficient between the number of episodes of nocturia and mean global PSQI was 0.42 (p<0.01). CONCLUSIONS: Patients with nocturia showed poor sleep quality, and this was related to the number of episodes of nocturia. This suggests that nocturia has a strong impact on sleep quality in patients with LUTS/BPH.

Organotypic Spinal Cord Slice Culture to Study Neural Stem/Progenitor Cell Microenvironment in the Injured Spinal Cord

The molecular microenvironment of the injured spinal cord does not support survival and differentiation of either grafted or endogenous NSCs, restricting the effectiveness of the NSC-based cell replacement strategy. Studying the biology of NSCs in in vivo usually requires a considerable amount of time and cost, and the complexity of the in vivo system makes it difficult to identify individual environmental factors. The present study sought to establish the organotypic spinal cord slice culture that closely mimics the in vivo environment. The cultured spinal cord slices preserved the cytoarchitecture consisting of neurons in the gray matter and interspersed glial cells. The majority of focally applied exogenous NSCs survived up to 4 weeks. Pre-exposure of the cultured slices to a hypoxic chamber markedly reduced the survival of seeded NSCs on the slices. Differentiation into mature neurons was severely limited in this co-culture system. Endogenous neural progenitor cells were marked by BrdU incorporation, and applying an inflammatory cytokine IL-1beta significantly increased the extent of endogenous neural progenitors with the oligodendrocytic lineage. The present study shows that the organotypic spinal cord slice culture can be properly utilized to study molecular factors from the post-injury microenvironment affecting NSCs in the injured spinal cord.

Efficacy and Safety during the Combination Therapy of Imipramine and Desmopressin in Primary Monosymptomatic Nocturnal Enuresis

PURPOSE: Nocternal enuresis is a common disorder. Tricyclic antidepressant and desmopressin have been accepted pharmacological treatment for this disorder. We conducted a cooperative study to investigate the efficacy and adverse reactions of imipramine, desmopressin and combination treatment in children with primary monosymptomatic nocturnal enuresis(PMNE). METHODS: Data from a large multicenter study were analysed. In the period of 8 months in 2002, the study comprised of 168 children(78 boys and 90 girls, 5 to 15 years old) with PMNE for imipramine, desmopressin or combination treatment. Before treatment a history, physical examination and laboratory tests were performed and the children were observed for 2 weeks. Response rate, adverse reactions and enuresis episodes after stopping drug administration were evaluated after 12-weeks of imipramine, desmopressin or combination of both. RESULTS: After 4 weeks, the frequency of bed wetting in all treated patients decreased during treatment significantly. Even though a 30-50% reduction in the number of wet nights were 68.6%, 74.4% and 86.1% during 12 weeks treatment by imipramine, desmopressin and both of them respectively, there was no significant difference between them. The most common adverse reaction was decreased appetite from imipramine administration. But no serious drug-related adverse events were reported. CONCLUSION: Efficacy of the combination therapy of imipramine and desmopressin in PMNE appears not to be better than either drug alone. It is necessary to pay attention on account of adverse reactions during imipramine treatment even though imipramine and desmopressin were generally well tolerated.

A Case of Pseudohypoparathyroidism Type II 1

Pseudohypoparathyroidism is characterized by target cell resistance to the effects of parathyroid hormone and classified into various types depending on the phenotypic and biochemical findings. Pseudohypoparathyroidism type II differs from type I in that the urinary excretion of cAMP is elevated both in the basal state and after stimulation with PTH. We experienced a case of pseudohypoparathyroidism type II in 12year old man who had generalized seizure. He had hypocalcemia, hyperphosphatemia, elevated serum PTH level and urinary basal cAMP. Also he had a normal phenotypic appearance. Bilateral basal ganglia calcifications was detected by CT scan.

A Case of Pseudohypoparathyroidism Type II 1

Pseudohypoparathyroidism is characterized by target cell resistance to the effects of parathyroid hormone and classified into various types depending on the phenotypic and biochemical findings. Pseudohypoparathyroidism type II differs from type I in that the urinary excretion of cAMP is elevated both in the basal state and after stimulation with PTH. We experienced a case of pseudohypoparathyroidism type II in 12year old man who had generalized seizure. He had hypocalcemia, hyperphosphatemia, elevated serum PTH level and urinary basal cAMP. Also he had a normal phenotypic appearance. Bilateral basal ganglia calcifications was detected by CT scan.