Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
Animals ; Autoimmune Diseases ; Biomarkers ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Humans ; Immunization ; Immunohistochemistry ; Inflammation ; Mice* ; Multiple Sclerosis ; Myelin Sheath ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Recurrence ; Spinal Cord ; Tacrolimus*

BACKGROUND: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). METHODS: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. RESULTS: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. CONCLUSIONS: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.
Amyotrophic Lateral Sclerosis* ; Animals ; Apoptosis ; Autophagy ; Cellular Structures ; Disease Progression ; Humans ; Mice* ; Mice, Transgenic ; Motor Neurons ; Neuroprotective Agents* ; Rotarod Performance Test ; Sirolimus*

In this study, to understand the pathogenesis of new rabbit hemorrhagic disease virus (RHDVa) serotype, we carried out to administrate RHDVa to rabbits, and to examine sequential electron microscopic changes and relationship between pathogenesis and apoptosis. TUNEL-positive cells began to be observed from 24 hours after inoculation (HAI) and the number of positive cells was slightly increased with the course of time. Whereas marked increase of positive cells was seen in the liver from the rabbits died acutely. Typical viral particles with cup-like projections and a diameter of 30~40 nm were detected in homogenized liver samples and tissues at 36 and 48, and 48 HAI, respectively. Ultrastructurally, glycogen deposition was observed from the first stage of hepatocellular degeneration by RHDVa infection and then, swelling and disruption of cristae of mitochondria by viral particles, swelling of smooth endoplasmic reticulum, vacuoles and vesicles were detected. Condensation, margination and fragmentation of chromatin were observed in degenerative hepatocytes at 36 and 48 HAI, indicating apoptotic bodies. These data offer that hepatocytic apoptosis by RHDV infection could be closely related with mitochondrial impairment in the hepatocytes.
Apoptosis ; Chromatin ; Electrons ; Endoplasmic Reticulum, Smooth ; Glycogen ; Hemorrhagic Disease Virus, Rabbit ; Hepatocytes ; Liver ; Mitochondria ; Rabbits ; Sprains and Strains ; Vacuoles ; Virion

Rabbit hemorrhagic disease is a highly acute and fatal viral disease caused by rabbit hemorrhagic disease virus (RHDV). Since first outbreak in Korea 1987, RHDV has been continually affected in the country, but the pattern of outbreak seem to be changed. In this study, to understand the pathogenesis of the new RHDVa serotype, we therefore carried out to inoculate RHDVa to rabbits, and to examine the sequential histopathologic changes and viral distribution. Macroscopically, various sized dark red or white spots or appearance were observed in the liver, lung, kidney uterus and ureter. In euhanized rabbits, significant pathologic findings such as infiltration of heterophils and mononuclear cells were observed at 24 hours after inoculation (HAI), and these were sequentially extended periportal to centrilobular area. However, in dead rabbits, severe hepatic degeneration and/or necrosis with relatively weak inflammatory responses were observed. RHDV antigens began to detect in liver, spleen, and lung from 12 HAI by PCR. Immunohistochemically, RHDV positive cells were seen in only liver from 24 HAI, and the degree of immunogen reactivity was stronger in dead rabbits than in euthanized ones. In conclusion, RHDVa caused the subacute or chronic infection accompanying low mortality and moderate to severe inflammatory reaction in rabbits, suggesting the possibility that RHD could become endemic.
Dental Caries ; Hemorrhagic Disease Virus, Rabbit ; Kidney ; Korea ; Liver ; Lung ; Necrosis ; Polymerase Chain Reaction ; Rabbits ; Spleen ; Sprains and Strains ; Ureter ; Uterus ; Virus Diseases

PURPOSE: There is a dearth of information on maternal drug exposure during lactation. The Korean Mothersafe Professional Counseling Center launched helpline to provide information and clinical consultation service on drug safety during lactation as well as in pregnancy. Here, we reviewed our 5 years' experience of counseling with drug exposed breastfeeding mothers. METHODS: The questionnaires were given to drug exposed breastfeeding mothers from January 2005 to April 2010 who contacted our helpline and follow-up survey data was collected by phone call. The questionnaires included lists of symptoms that exposed mothers experienced and that was observed in their infants, as well as demographic questions and questions about lactation. RESULTS: A total of 278 mothers completed the survey and lactational exposure was estimated. Majority of them reported that their infants and themselves never experienced serious side effects of drugs during lactation. Only 3 (1.1%) babies reported side effects and 20 (7.2%) mothers reported decreased production of breast milk. Two hundred thirty two (83.5%) mothers continued breastfeeding after counseling. Lactation was stopped temporarily in 20 (7.2%) mothers and permanently in 26 (9.3%) mothers. CONCLUSION: Most of the drugs exposed during lactation did not cause serious side effects to infants and mothers. As many drugs have inadequate data to assure safety, the clinician is left with a dilemma as to where the balance of risks and benefits lie with respect to the mother and her baby. The author expect that analyses of these counseling will contribute to provide practical answers to clinicians as well as exposed mothers and to establish correct breastfeeding practice.
Breast Feeding ; Counseling ; Female ; Follow-Up Studies ; Humans ; Infant ; Lactation ; Milk, Human ; Mothers ; Pregnancy ; Surveys and Questionnaires ; Risk Assessment

Localized scleroderma is a connective tissue disorder characterized by thickening and fibrosis of the skin due to excessive collagen deposition in the dermis. Dystrophic calcinosis occurs when calcium is deposited in the previously damaged skin tissue, and calcium and phosphorous levels in the blood are within normal limits. It occurs secondary to connective tissue disease, infection, inflammatory processes, chronic venous stasis, cutaneous neoplasm, and trauma. We report a rare case of dystrophic calcinosis cutis with transepidermal elimination secondary to localized scleroderma.
Calcinosis ; Calcium ; Collagen ; Connective Tissue ; Connective Tissue Diseases ; Dermis ; Fibrosis ; Scleroderma, Localized ; Skin

BACKGROUND: Acute colonic pseudo-obstruction (ACPO) refers to dilatation of the colon and decreased bowel motility without evidence of mechanical obstruction. Neostigmine, an acetylcholinesterase inhibitor, has been used in patients in whom supportive therapy failed to resolve ACPO. Here, we report the results of administering neostigmine to treat ACPO in children with hematologic malignancies. METHODS: Between September 2005 and December 2009, 10 patients (8 male and 2 female) were diagnosed with ACPO at the Department of Pediatrics, Catholic University of Korea. Diagnosis of ACPO was based on typical clinical features as well as colonic dilatation found on abdominal CT imaging. Neostigmine was administered subcutaneously at a dosage of 0.01 mg/kg/dose (maximum 0.5 mg) twice daily for a maximum of 5 total doses. ACPO was determined to be responsive to neostigmine if the patient showed both stool passage and improvement of clinical symptoms. RESULTS: The study group included 8 acute lymphoblastic leukemia patients, 1 patient with malignant lymphoma, and 1 patient with juvenile myelomonocytic leukemia. The median age at ACPO diagnosis was 8.5 years (range, 3-14). Overall, 8 patients (80%) showed therapeutic response to neostigmine at a median of 29 hours after the initial administration (range, 1-70). Two patients (20%) showed side effects of grade 2 or above, but none complained of cardiovascular symptoms that required treatment. CONCLUSION: In this study, ACPO was diagnosed most often in late-childhood ALL patients. Subcutaneous neostigmine can be used to effectively treat ACPO diagnosed in children with hematologic malignancies without major cardiovascular complications.
Acetylcholinesterase ; Child ; Colon ; Colonic Pseudo-Obstruction ; Dilatation ; Hematologic Neoplasms ; Humans ; Korea ; Leukemia, Myelomonocytic, Juvenile ; Lymphoma ; Male ; Neostigmine ; Pediatrics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

PURPOSE: Ibuprofen is a non steroidal anti-inflammatory drug used for treating fever and pain including headache, arthralgia, and back pain. There is scarce information on the safety of ibuprofen associated with fetal anomaly when used early in pregnancy. Epidemiology studies have suggested that use of NSAIDs, including ibuprofen, during pregnancy may increase the risk of cardiac defects and gastroschisis. The aim of the study was to evaluate fetal outcomes among pregnant women who were unintentionally exposed to ibuprofen in early pregnancy. METHODS: Total 381 pregnant women who were unintentionally exposed to ibuprofen during early pregnancy were prospectively followed up. In addition, 643 age and gravity matched pregnant women not exposed to any potential teratogenic agent during pregnancy were recruited as controls. Patients were followed-up until delivery or loss to follow-up. Newborns were examined in order to identify any major congenital malformation. RESULTS: Mean age of exposed women was 31.2+/-3.4 years, with a mean number of previous pregnancies of 2.3+/-1.2 and mean gestational weeks at exposure of 4.4+/-2.2. All gestations were confirmed by ultrasonography. Of exposed women, 17 (5.6%) had spontaneous abortions, 16 were on- going pregnancies, 1 had an intra-uterine fetal death, 21 artificial abortion and 55 cases were lost to follow-up. Therefore, 271 pregnancies unintentionally exposed to ibuprofen were evaluated, each delivering a singleton baby. Three babies had congenital anomalies: one had unilateral hydronephrosis, another baby was born with a unilateral inguinal hernia. The last baby was born with unilateral kidney dysplasia with megaureter. In the control group, 6 babies were born with major malformations [1.11% vs. 1.31% (P=0.552, OR: 0.841, 95% CI: 0.2 to 3.4)]. CONCLUSION: These preliminary results suggest that the ibuprofen may not be a major human teratogen.
Abortion, Spontaneous ; Anti-Inflammatory Agents, Non-Steroidal ; Arthralgia ; Back Pain ; Female ; Fetal Death ; Fever ; Follow-Up Studies ; Gastroschisis ; Gravitation ; Headache ; Hernia, Inguinal ; Humans ; Hydronephrosis ; Ibuprofen ; Infant, Newborn ; Kidney ; Lost to Follow-Up ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, First ; Pregnant Women ; Prospective Studies

Choledochal cysts in neonates and young infants take two forms: the choledochal cyst associated with biliary atresia (CCBA) and the choledochal cyst in the absence of biliary atresia (CC). Infants in both groups usually have similar clinical symptoms at presentation, but management and prognosis are different. While early portoenterostomy is required for CCBA, cyst excision with hepaticojejunostomy or choledochojejunostomy is usually performed for CC. The former shows a relatively poor prognosis, and the latter shows a better prognosis. Two infants who presented with clinical features of neonatal cholestasis, and clinically suspected to have choledochal cysts, were found on imaging studies and surgery to have extrahepatic bile duct atresia in association with choledochal cysts.
Bile Ducts, Extrahepatic ; Biliary Atresia* ; Choledochal Cyst* ; Choledochostomy ; Cholestasis ; Humans ; Infant ; Infant, Newborn ; Prognosis

Henoch-Schonlein purpura is a systemic leukoclastic vasculitis and involves small vessels resulting in vasculitis. Major pathogenetic mechanism of Henoch-Schonlein purpura has not been still elucidated. Possible causes, however, may be associated with viral infection, bacterial infection, exposure to drugs and toxins, systemic diseases and carcinomas. Henoch-Schonlein purpura rarely develops in patients with tuberculosis, though there have been some reports on the development of this syndrome during antituberculous therapy. A 24-year-old man was admitted to our hospital because of diffuse abdominal pain, lower leg purpura and disseminated tuberculosis involving lung, duodenum, colon and lumbar spine and diagnosed as Henoch-Schonlein purpura with disseminated tuberculosis. Henoch-Schonlein purpura developed before antibuberculous therapy and antituberculous treatment was effective both in disseminated tuberculosis and Henoch-Schonlein purpura. We concluded that disseminated tuberculosis might be a cause of Henoch-Schonlein purpura.
Abdominal Pain ; Bacterial Infections ; Colon ; Duodenum ; Humans ; Leg ; Lung ; Purpura ; Purpura, Schoenlein-Henoch* ; Spine ; Tuberculosis* ; Vasculitis ; Young Adult