Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.

Neuronal firing patterns and frequencies determine the nature of encoded information of the neurons. Here we discuss the molecular identity and cellular mechanisms of spike-frequency adaptation in central nervous system (CNS) neurons. Calcium-activated potassium (K(Ca)) channels such as BK(Ca) and SK(Ca) channels have long been known to be important mediators of spike adaptation via generation of a large afterhyperpolarization when neurons are hyper-activated. However, it has been shown that a strong hyperpolarization via these KCa channels would cease action potential generation rather than reducing the frequency of spike generation. In some types of neurons, the strong hyperpolarization is followed by oscillatory activity in these neurons. Recently, spike-frequency adaptation in thalamocortical (TC) and CA1 hippocampal neurons is shown to be mediated by the Ca²⁺-activated Cl- channel (CACC), anoctamin-2 (ANO2). Knockdown of ANO2 in these neurons results in significantly reduced spike-frequency adaptation accompanied by increased number of spikes without shifting the firing mode, which suggests that ANO2 mediates a genuine form of spike adaptation, finely tuning the frequency of spikes in these neurons. Based on the finding of a broad expression of this new class of CACC in the brain, it can be proposed that the ANO2-mediated spike-frequency adaptation may be a general mechanism to control information transmission in the CNS neurons.
Action Potentials ; Brain ; Central Nervous System* ; Fires ; Neurons* ; Potassium ; Potassium Channels, Calcium-Activated

Acute necrotizing esophagitis (AEN), also called "black esophagus," is a rare disorder with an unknown pathogenesis. Endoscopic findings generally show black pigmentation throughout the esophagus. This case also offered rare views of the gross anatomy of this disorder. Histological examination revealed that the mucosal and submucosal layers of the esophagus were involved in the severe necrotizing inflammation. The chief manifestation of this disease is hematemesis from hemorrhage of the upper gastrointestinal tract with a typically multifactorial etiology. AEN is also characterized by a clear boundary at the gastroesophageal junction where the necrosis stops. In this study, we report an autopsy case of a 61-year-old man with necrotizing inflammation throughout the esophagus and esophageal necrosis from the laryngopharynx to the gastroesophageal junction. The patient was a disabled person with a history of alcohol abuse who was also diagnosed with mild coronary arteriosclerosis and fatty liver on the basis of the underlying diseases. In this case, the main etiology for poor perfusion from the distal esophageal area was likely underlying illness, history of alcoholism, and malnutrition.
Alcoholism ; Autopsy* ; Coronary Artery Disease ; Disabled Persons ; Esophagitis* ; Esophagogastric Junction ; Esophagus ; Fatty Liver ; Hematemesis ; Hemorrhage ; Humans ; Hypopharynx ; Inflammation ; Malnutrition ; Middle Aged ; Necrosis ; Perfusion ; Pigmentation ; Upper Gastrointestinal Tract

Pulmonary edema is a potentially life-threatening complication of acute airway obstruction. Occasionally, patients experience sudden, unexpected and severe pulmonary edema during treatment of upper airway obstruction. Two forms of postobstructive pulmonary edema (POPE) have been identified. Type I POPE follows a sudden, severe episode of upper airway obstruction and type II POPE develops soon after the relief of chronic upper airway obstruction. The pathogenesis of POPE is multifactorial. The application of moderate continuous positive airway pressure in conjunction with the administration of diuretics usually clears pulmonary edema in these clinical settings within 24 hours. Awareness of this uncommon condition is crucial for the otolaryngologist to make an early diagnosis and initiate successful treatment. We present two cases of postobstructive pulmonary edema after treatment for upper airway obstruction.
Airway Obstruction ; Continuous Positive Airway Pressure ; Diuretics ; Early Diagnosis ; Humans ; Pulmonary Edema*

Anoctamin 2 (ANO2 or TMEM16B), a calcium-activated chloride channel (CaCC), performs diverse roles in neurons throughout the central nervous system. In hippocampal neurons, ANO2 narrows action potential width and reduces postsynaptic depolarization with high sensitivity to Ca2+ at relatively fast kinetics. In other brain regions, including the thalamus, ANO2 mediates activity-dependent spike frequency adaptations with low sensitivity to Ca2+ at relatively slow kinetics. How this same channel can respond to a wide range of Ca2+ levels remains unclear. We hypothesized that splice variants of ANO2 may contribute to its distinct Ca2+ sensitivity, and thus its diverse neuronal functions. We identified two ANO2 isoforms expressed in mouse brains and examined their electrophysiological properties: isoform 1 (encoded by splice variants with exons 1a, 2, 4, and 14) was expressed in the hippocampus, while isoform 2 (encoded by splice variants with exons 1a, 2, and 4) was broadly expressed throughout the brain, including in the cortex and thalamus, and had a slower calcium-dependent activation current than isoform 1. Computational modeling revealed that the secondary structure of the first intracellular loop of isoform 1 forms an entrance cavity to the calcium-binding site from the cytosol that is relatively larger than that in isoform 2. This difference provides structural evidence that isoform 2 is involved in accommodating spike frequency, while isoform 1 is involved in shaping the duration of an action potential and decreasing postsynaptic depolarization. Our study highlights the roles and molecular mechanisms of specific ANO2 splice variants in modulating neuronal functions.

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 microm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.
Ambulatory Care Facilities ; Basophils ; Biopsy ; Colon ; Colonoscopy ; Cytoplasm ; Eosinophils ; Exudates and Transudates ; Female ; Gastrointestinal Tract ; Histiocytes ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; Kidney ; Kidney Transplantation ; Lymphocytes ; Malacoplakia ; Plasma Cells ; Polyps ; Transplants

We report a case of a chronic hemodialysis patient who developed hypermagnesemia due to an overdose of magnesium-containing laxative and paralytic ileus resulting in colonic perforation. Despite intravenous calcium infusion and daily hemodialysis, the patient developed ischemic colitis and intestinal perforation. Colonic perforation accompanied with hypermagnesemia in hemodialysis patients has rarely been reported. This case suggests that hypermagnesemia should be considered in renal failure patients as this can result in life-threatening events despite prompt treatment.
Colitis, Ischemic/*chemically induced/diagnosis/surgery ; Constipation/*drug therapy/surgery ; Female ; Humans ; Intestinal Perforation/*chemically induced/surgery ; Laxatives/adverse effects/*poisoning ; Magnesium/*poisoning ; Middle Aged ; *Renal Dialysis

BACKGROUND: Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies. METHODS: Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed. RESULTS: Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29-32 weeks) than in singleton placentas (33-36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p=.052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p<.05). CONCLUSIONS: The higher frequency of non-basal VUE in twin placentas and of CCA in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti-fetal rejection related to increased fetal antigens in twin pregnancies. The peak of CCA at an earlier gestational age in twin placentas than in singleton placentas suggests that CCA is influenced by placental maturation.
Chorioamnionitis ; Eosine Yellowish-(YS) ; Female ; Gestational Age ; Hematoxylin ; Humans ; Inflammation* ; Placenta ; Pregnancy ; Pregnancy, Twin* ; Premature Birth ; Republic of Korea ; Seoul ; Twins*

The incidence, recurrence, and mortality of Clostridium difficile infection are increasing and the standard therapy is oral metronidazole or vancomycin. Since treatment failure with standard therapy is increasing, an alternative therapy is needed. Fecal microbiota transplantation is one effective method in patients with refractory or recurrent C. difficile infection, including pseudomembranous colitis. Here, we report two cases of refractory pseudomembranous colitis treated with fecal microbiota transplantation.
Clostridium difficile ; Enterocolitis, Pseudomembranous ; Humans ; Incidence ; Metagenome ; Metronidazole ; Recurrence ; Transplants ; Treatment Failure ; Vancomycin

Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in ZNF462 gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (−3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.