Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4-5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1-/- Per2-/- mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function.

Panhypopituitarism due to craniopharyngioma with bilateral slipped capital femoral epiphysis / 영남의대학술지

Craniopharyngiomas are rare primary intracranial tumors. Despite their benign histological appearance, they are often associated with an unfavorable prognosis. The typical manifestations upon diagnosis are headache, visual impairment, polyuria/polydypsia, growth retardation, disturbance of pubertal development, and significant weight gain. The treatment options include radical surgery or radiotherapy, or a combination of these modalities. Slipped capital femoral epiphysis (SCFE) is the most common adolescent hip disorder. SCFE occurs when the capital femoral epiphysis displaces posteriorly on the femoral neck at the level of the physis. The etiology of SCFE is thought to be multifactorial and may include obesity, growth surges, and less common endocrine disorders. The related endocrine disorders include hypothyroidism, growth hormone supplementation, hypogonadism, and panhypopituitarism. Reported herein is a case of panhypopituitarism caused by craniopharyngioma combined with SCFE.

Spontaneous Spinal Epidural Hematoma Caused by Dual Antiplatelet Agent Therapy after Percutaneous Coronary Intervention / 대한내과학회지

Spontaneous spinal epidural hematomas (SSEH) are rare, accounting for less than 1% of all spinal epidural lesions. The potential causes include coagulopathies, antithrombotic drugs, hypertension, increased venous pressure, and vascular malformations. A SSEH causes severe neurological deficits unless treated in a timely manner. As the number of patients who are diagnosed with ischemic heart disease and treated using percutaneous coronary intervention (PCI) increases, the prescription of dual antiplatelet agents is also increasing. We report a case of SSEH caused by dual antiplatelet agent therapy in a patient who had undergone PCI.

Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype

We report the case of a patient who experienced extreme recurrent gestational hyperlipidemia. She was diagnosed with partial lipoprotein lipase (LPL) deficiency but without an associated LPL gene mutation in the presence of the apolipoprotein E3/2 genotype. This is the first reported case of extreme gestational hyperlipidemia with a partial LPL deficiency in the absence of an LPL gene mutation and the apolipoprotein E 3/2 genotype. She was managed with strict dietary control and medicated with omega-3 acid ethyl esters. A patient with extreme hyperlipidemia that is limited to the gestational period should be considered partially LPL-deficient. Extreme instances of hyperlipidemia increase the risk of acute pancreatitis, and the effect of parturition on declining plasma lipid levels can be immediate and dramatic. Therefore, decisions regarding the timing and route of delivery with extreme gestational hyperlipidemia are critical and should be made carefully.

Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6

Low density lipoprotein receptor (LDLR) plays an important role in the cholesterol homeostasis. We examined the possible circadian regulation of LDLR and mechanism(s) underlying it. In mice, blood glucose and plasma triglyceride, total and high density lipoprotein cholesterol varied distinctively throughout a day. In addition, LDLR mRNA oscillated in the liver in a functional clock-dependent manner. Accordingly, analysis of human LDLR promoter sequence revealed three putative E-boxes, raising the possible regulation of LDLR expression by E-box-binding transcription factors. To test this possibility, human LDLR promoter reporter constructs were transfected into HepG2 cells and the effects of CLOCK/BMAL1, Hes1, and Hes6 expression were analyzed. It was found that positive circadian transcription factor complex CLOCK/BMAL1 upregulated human LDLR promoter activity in a serum-independent manner, while Hes family members Hes1 and Hes6 downregulated it only under serum-depleted conditions. Both effects were mapped to proximal promoter region of human LDLR, where mutation or deletion of well-known sterol regulatory element (SRE) abolished only the repressive effect of Hes1. Interestingly, hes6 and hes1 mRNA oscillated in an anti-phasic manner in the wild-type but not in the per1-/-per2-/- mouse. Comparative analysis of mouse, rat and human hes6 genes revealed that three E-boxes are conserved among three species. Transfection and site-directed mutagenesis studies with hes6 reporter constructs confirmed that the third E-box in the exon IV is functionally induced by CLOCK/BMAL1. Taken together, these results suggest that LDLR expression is under circadian control involving CLOCK/BMAL1 and Hes family members Hes1 and Hes6.

Circadian Rhythms in Urinary Functions: Possible Roles of Circadian Clocks? / 대한배뇨장애요실금학회지

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.

Circadian Rhythms in Voiding Function and Dysfunction / 대한배뇨장애요실금학회지

While circadian rhythms in fluid intake, urine production, and urine storage have been substantiated in diurnal human and nocturnal rodents, the mechanism(s) underlying it is largely unknown. With the elucidations of molecular clockwork and its functional significance in mammals, new opportunities arise to investigate possible circadian control of voiding function and dysfunction, which undoubtedly needs immediate attentions of researchers in the field.

Isolated Congenital Incus Anomaly / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A non-progressive and conductive hearing loss with normal eardrum, which has no history of trauma and infection is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, the most common anomalous ossicle is stapes. However, incus anomaly is sometimes encountered with or without stapes anomaly. The objectives of this study are to describe patterns of incus anomaly, encountered in patients who have a normal eardrum and to analyze their surgical results with special reference to the patterns of incus anomaly. SUBJECTS AND METHOD: We reviewed 26 patients (31 ears) with congenital incus anomaly, which were confirmed through exploratory tympanotomy at Ajou University Hospital from 1994 to 2005. We analyzed temporal bone CT, preoperative and postoperative audiometric findings, and surgical findings. RESULTS: 10 anomalous patterns were detected out of 31 cases of congenital incus anomaly. Incus without its long process was the most common anomalous pattern. In 15 out of 26 cases (57.7%), incus anomaly was associated with stapes anomaly, which was usually unilateral. We could get hearing improvement in 26 out of 31 ears (89.1%). CONCLUSION: Various anomalous patterns of incus were noted in our series. Incus anomaly was often associated with stapes anomaly, which was usually unilateral. The surgical result of incus anomaly was excellent except the cases without stapes.

Congenital Stapes Anomalies with Normal Eardrum

OBJECTIVES: A non-progressive and conductive hearing loss with normal eardrum, but no history of trauma and infection, is highly suggestive of a congenital ossicular malformation. Among ossicular anomalies, stapes anomaly is the most common. The purpose of this study is to describe patterns of stapes anomaly and to analyze its surgical outcome with special reference to its patterns. METHODS: We conducted a retrospective case review. The subjects comprised 66 patients (76 ears) who were decisively confirmed by the exploratory tympanotomy as congenital stapes anomalies without any anomalies of the tympanic membrane and external auditory canal. The preoperative and postoperative audiological findings, temporal bone computed tomography scan, and operative findings were analyzed. RESULTS: There were 16 anomalous patterns of stapes among which footplate fixation was the most common anomaly. These 16 patterns were classified into 4 types according to the status of stapes footplate. Successful hearing gain was achieved in 51 out of 76 ears (67.1%) after surgical treatment. CONCLUSION: Footplate fixation was usually bilateral, whereas stapes anomalies associated with other ossicular anomaly were usually unilateral. The success of the surgical treatment of stapes anomaly might depend on its developmental status of the footplate. Stapes anomalies were detected without any fixed patterns, therefore, it is quite possible to detect a large variety of patterns in future.

Management for the Children with Otitis Media with Effusion in the Tertiary Hospital

OBJECTIVES: Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study. METHODS: Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months. RESULTS: Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05). CONCLUSION: In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/ obese (BMI > or =23) and 145 normal (BMI 18 to <23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

Digital Silver for Well Ageing

No abstract available.

Three-dimensional Computer-aided Reconstruction of the Temporal Bone in Mongolian Gerbil / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The natural progress of experimentally induced diseases of the temporal bone can be more precisely observed using the 3-dimensional reconstructive technique. We therefore established a method by generating three-dimensional images of the temporal bone with histologic specimen, and measured the structures in the temporal bone of mongolian gerbil in three dimensions. MATERIALS AND METHOD: One mongolian gerbil(Meriones unguiculatus) of 5 weeks old was studied. Temporal bone specimen was processed for histologic study and reference marks were made in each paraffin block to permit accurate alignment. The embedded specimen was horizontally sectioned at 10 micrometer interval. Each histology section was digitalized and a total of 450 image data were entered to the computer software by tracing each region of interest with digitizer. RESULTS: We reconstructed 3-dimensional images of the cochlea, semicircular canals, and facial nerve. For the semicircular canals, we measured the width and height of each canal and angles between canals. For the cochlea, we measured the diameter of each turn and the volume. For the facial nerve, we measured the length of each segment and the angles between neighboring segments. CONCLUSION: In our study, we successfully reconstructed 3-dimensional images of the inner ear structures and facial nerve, and carried out a quantitative analysis of those structures. Applying this 3-dimensional reconstructive technique to disease-induced animal model, we would evaluate the progress of specific disease and the efficacy of treatment more accurately.

A Case of Actinomycosis Arising in Parotid Gland / 대한이비인후과학회지

Actinomycosis is an unusual granulomatous infection caused by gram-positive organisms (Actinomycetes. israelii, A. naeslundii, A. odontolyticus, and A. viscosus). Depending on the involved anatomical region, actinomycosis is classified into three clinical forms: cervicofacial (the most common, 55%), thoracic, or abdominopelvic. It is still a rare disease constituting less than 1% of all infections and primary parotid actinomycosis is even more rare, indeed. Actinomycosis typically has a chronic, indolent course characterized by swelling and induration of the soft tissues and eventual spontaneous drainage through multiple sinus tracts. The sulfur granule defines the pathognomonic pathologic finding of actinomycosis, but it has been reported in only 40% of cases. Treatment of cervicofacial actinomycosis consists of: removal of the infectious source, such as an infected tooth; incision and drainage, ideally including irrigating drains, and appropriate use of antibiotics and surgery. Our case dealt with a 55-year-old female presenting a firm mass in right parotid area. She was treated with surgical excision and antibiotic treatment.

The Inhibitory Mechanism of N-(4-Hydroxyphenyl) Retinamide on Prostaglandin E2 Synthesis in Squamous Cell Carcinoma Cell Line / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: It is well known that Prostaglandin E2 (PGE2) is the most predominant prostaglandin in squamous cell carcinoma and that PGE2 synthesis is suppressed by retinoid. The purpose of this study was to confirm whether (N-4-Hydroxyphenyl) retinamide (N-4-HPR) suppressed PGE2 synthesis, and investigate its inhibitory mechanism on PGE2 synthesis in squamous cell carcinoma. MATERIALS AND METHOD: MDA 886Ln was used as the squamous cell carcinoma cell line. We evaluated the effects of four retinoids (all-trans-RA, 13-cis-RA, retinyl acetate, and N-4-HPR) on PGE2 synthesis: the effect of N-4-HPR concentration on PGE2 synthesis and Cox-2 mRNA, the effect of N-4-HPR on Cox-2 protein, and the effect of N-4-HPR on the cyclooxygenase activity. RESULTS: Among the four retinoids, N-4-HPR was the most potent suppressor of PGE2 synthesis. N-4-HPR suppressed PGE2 synthesis, but N-4-HPR did not suppress Cox-2 mRNA or Cox-2 protein. Cyclooxygenase activity was suppressed by N-4-HPR. CONCLUSION: With these results, we suggest that the inhibitory mechanism of N-4-HPR on the PGE2 synthesis may be suppression of the cyclooxygenase activity, and Cox-2 mRNA and protein were not suppressed by N-4-HPR.

Combination of Mutated Herpes Simplex Virus (G207) with Radiation for the Treatment of Squamous Cell Carcinoma of the Head and Neck / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: G207 virus is an ideal candidate of oncolytic viral therapy. It is a multi-gene mutant of HSV-1 with a deletion at the gamma34.5 loci and a LacZ gene insertion in the ICP6 gene, encoding the HSV ribonucleotide reductase. Ionizing radiation induces the growth arrest-inducible gene, Gadd34, a protein that correlates with apoptosis following radiation and has homology with the G207 gamma34.5 gene. It is hypothesized that the combination of radiotherapy with G207 virus may have a synergic effect on viral replication and efficacy. The purpose of this study is to evaluate the combination of the cytotoxic G207 virus with radiation therapy to treat head and neck tumors. MATERIALS AND METHOD: Five human SCCHN cell lines and one murine SCC cell line were utilized in this study. There were two groups of cells: control cells received no irradiation while the second group was irradiated with 400 cGy. Cells were infected with G207 vectors at a multiplicity of infection (MOI) of 0.1. Cytotoxicity assay was performed for 5 days. Cells and culture medium supernatant were collected and viral titers determined by plaque forming units on Vero cells. To evaluate infection efficiency, X-gal staining was performed at 24hr post infection. RESULTS: All head and neck squamous cancer cell lines tested demonstrated an increased susceptibility to the combination of G207 virus with radiation therapy when compared with each single modality (more than additive effect, p<0.05). Even though cell lines such as SCC25, MSKQLL2, or SCCVII were radioresistant, the combination of G207 with radiation therapy showed significantly increased cytotoxic effect. X-gal staining and viral growth curve studies demonstrated that G207 replications in radiated cell lines were not decreased as compared with non-radiated ones. CONCLUSION: The results provide preliminary support for the use of G207 oncolytic virus as a radiation adjuvant in treatment of head and neck cancer. The combination of radiation and oncolytic viral gene therapy may eventually be useful in treating patients with radio-resistant, non-resectable disease, and patients with a high probability of contracting postoperative microscopic residual diseases.

Effect of Etiologic Factors on Prognosis of Hearing Recovery in Sudden Deafness / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There are lots of debates regarding the prognostic factors in sudden deafness patients. The aim of this study is to identify prognostic factors that might be associated with the degree of hearing recovery from sudden deafness. MATERIALS AND METHOD: We reviewed the records of 110 patients who were admitted for treatment between 1999 and 2001 under the initial diagnosis of idiopathic sudden hearing loss. Patients were classified into following subgroups based on the data of our own diagnostic protocol, including history taking, physical examination and laboratory tests: cardiovascular hematologic group, infectious group, metabolic group, immunologic group, cochlear neurologic group, and the other group. RESULTS: Patients who had cardiovascular hematologic factors and cochlear neurologic factors showed lower recovery rates than the other patients. Patients with metabolic factors showed higher recovery rate than those with other factors. CONCLUSION: These results suggest that cardiovascular hematologic factors and cochlear neurologic factors might be most significantly related with prognosis in sudden deafness patients.

Effectiveness of Cupulolith Repositioning Maneuver in the Treatment of Lateral Semicircular Canal Cupulolithiasis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There is still a controversy surrounding lesion side differentiation and treatment of the lateral canal cupulolithiasis. The purpose of this study is to understand side differentiation, and study the treatment of this disease through analyses of clinical features, electronystagmographic (ENG) results, treatment maneuvers and its effectiveness. MATERIALS AND METHODS: Twenty three patients who showed ageotropic direction-changing horizontal positional nystagmus were included in this study. A supine head turning test was performed to induce positional nystagmus. Clinical findings and typical features of the nystagmus were recorded. Neurologic examinations, ENG tests, and MRI (6 cases) were checked to exclude the possibility of any central lesions. Cupulolith Repositioning Maneuver (CuRM) was applied on the patients and these patients were instructed to keep the healthy side at the lateral decubitus position while sleeping. RESULTS: The nystagmus had a short latency, no fatigability, and persistency in character. In one patient, nystagmus was resolved spontaneously, so we could not decide the lesion side. However, seventeen out of 22 patients showed significant differences between the intensity of each side nystagmus, and all of them showed stronger nystagmus when the head was rotated to the unaffected side. In five patients who showed no significant difference between the intensity of each side nystagmus, two cases showed same results and three cases showed opposite results. Typical nystagmus and spinning sensation in the supine head-turning test had completely subsided after physical therapy. CONCLUSION: In the cupulolithiasis of lateral semicircular canal, ageotropic nystagmus was stronger when the pathological ear was at the uppermost position, and this excitatory nystagmus beat to the lesion side. But, if there was no significant difference between the intensity of each side nystagmus, associated canal paresis, other types of BPPV, past history of acute vestibuloneuritis, and Meniere's disease, etc. might be helpful to localize the lesion side. CuRM and post- treatment lateral decubitus position kept during the night (while sleeping on the day of treatment) were effective in treating the cupulolithiasis of lateral semicircular canal.