4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages

Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

Clinical Findings of Asymptomatic Carpal Tunnel Syndrome in Patients With Diabetes Mellitus

OBJECTIVE: To evaluate the clinical differences between patients with diabetes mellitus (DM) who have asymptomatic carpal tunnel syndrome (CTS) and those who have symptomatic CTS. METHODS: Sixty-three patients with DM were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ), nerve conduction studies (NCS), and ultrasonographic evaluation of the cross-sectional area (CSA) of the median nerve. According to the BCTQ responses and NCS results, the patients were divided into the following three groups: group 1 (n=16), in which NCS results did not reveal CTS; group 2 (n=19), in which NCS results revealed CTS but the group scored 0 points on the BCTQ (asymptomatic); and group 3 (n=28), in which NCS results revealed CTS and the group scored >1 point on the BCTQ (symptomatic). The clinical findings, NCS results, and CSA of the median nerve were compared among the three groups. RESULTS: There were no significant differences in age, DM duration, glycated hemoglobin levels, and presence of diabetic polyneuropathy among the three groups. The peak latency of the median sensory nerve action potential was significantly shorter in group 1 than in groups 2 and 3 (p<0.001); however, no difference was observed between groups 2 and 3. CSA of the median nerve at the carpal tunnel in group 2 was significantly larger than that in group 1 and smaller than that in group 3 (p<0.05). CONCLUSION: The results of our study suggest that the symptoms of CTS in patients with diabetes are related to CSA of the median nerve, which is consistent with swelling of the nerve.

Factors Affecting Performance of Hand Hygiene by Parents of Hospitalized Infants

PURPOSE: Purpose of this study was to identify factors affecting the performance of hand hygiene by parents of hospitalized infants. METHODS: The study was conducted with 209 parents of hospitalized infants from one hospital in Changwon. Data were collected from June through August, 2014 and analyzed using SPSS Win 18.0 program. RESULTS: There were positive correlations between performance of hand hygiene and perceptions of sanitary formula bottle (r=.586, p<.001), attitude to hand hygiene (r=.438, p<.001), and knowledge of hand hygiene (r=.405, p<.001) and between parent efficacy and perceptions of sanitary formula bottle (r=.572, p<.001). Awareness of perceptions of sanitary formula bottle (beta=.308, p<.001), parent efficacy (beta=.281, p<.001) and hand hygiene attitude (beta=.207, p<.001) were significant predictors of hand hygiene performance and explained 46.1% of the variance. CONCLUSION: To increase infection control medical institutions should provide education on hand hygiene and training for parents of hospitalized infants. In order to enhance the performance of hand hygiene, it is necessary to develop and apply nursing programs for hospitalized infants that include hand hygiene attitude, maintenance of the sanitary formula bottle and parent efficacy.

Holmes Tremor After Brainstem Hemorrhage, Treated With Levodopa

Holmes tremor is a rare movement phenomenon, with atypical low-frequency tremor at rest and when changing postures, often related to brainstem pathology. We report a 70-year-old female patient who was presented with dystonic head and upper limb tremor after brainstem hemorrhage. The patient had experienced a sudden onset of left hemiparesis and right facial paralysis. Brain magnetic resonance imaging showed an acute hemorrhage from the brachium pontis through the dorsal midbrain on the right side. Several months later, the patient developed resting tremor of the head and left arm, which was exacerbated by a sitting posture and intentional movement. The tremor showed a regular low-frequency (1-2 Hz) for the bilateral sternocleidomastoid and cervical paraspinal muscles at rest. The patient's symptoms did not respond to propranolol or clonazepam, but gradually improved with levodopa administration. Although various remedies were attempted, overall, the results were poor. We suggest that levodopa might be a useful remedy for Holmes tremor. The curative or relieving effect of the dopaminergic agent in Holmes tremor needs more research.

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.

Associations of IGF-I, IGFBP-3 on early Catch-up Growth in Small for Gestational Age Infants / 대한주산의학회잡지

OBJECTIVE: This study was aimed to analyze the effect of Insulin-like growth factor (IGF)-I and Insulin-like growth factor binding protein (IGFBP)-3 on early catch-up growth in small for gestational age (SGA) infants. METHODS: We prospectively studied in 18 SGA infants who were admitted at Chungnam National University Hospital from January 2004 to January 2006. We divided them into two groups of intrauterine growth retardation; symmetric and asymmetric type. Maternal and neonatal characteristics and the value of IGF-1 and IGFBP-3 at birth were compared between the two groups. After 12 months later, we checked their body weight and height to evaluate catch-up growth. RESULTS: Among 18 SGA infants, 5 were male and 13 were female. Average gestational age at birth was 38.4+/-1.1 weeks. Average birth weight was 2,359+/-154 g. Nine babies showed symmetric intrauterine growth retardation. Thirteen babies achieved catch-up growth at 12 month of age. There was no correlation between the characteristics of SGA and catch-up growth. However, the IGF-I and IGFBP-3 values were significantly higher in babies who showed catch-up growth. CONCLUSION: We were able to predict catch-up growth at early infancy by evaluating serum IGF-I and IGFBP-3 values at birth in SGA infants.

Effect of Etanercept on Steroid Refractory Graft-versus-host Disease in Children

BACKGROUND: Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in children with steroid-refractory acute GVHD (aGVHD) (n=5) and chronic GVHD (cGVHD) (n=3). METHODS: Five males and 3 females were enrolled and their median age was 14.4 years (range, 2.1~18.8). Etanercept 0.4 mg/kg per dose (maximum dose, 25 mg) was given subcutaneously twice weekly for 4 weeks followed by 0.4 mg/kg per dose (maximum dose, 25 mg) weekly for 4 weeks. At the time of initiation of etanercept, 5 patients had aGVHD grade III to IV (III=4, IV=1) and 3 patients had moderate to severe cGVHD (moderate=1, severe=2). RESULTS: Overall, 6 of 8 patients (75%) responded to the treatment with etanercept, including 5 patients with aGVHD [n=3 complete response (CR), n=2 partial response (PR)] and 1 patient with cGVHD [n=1 PR, n=2 no response (NR)]. Clinical responses were most commonly seen in patients with refractory gut aGVHD. CMV reactivation occurred in 2 patients, bacterial infection in 1 patient, and fungal infection in 1 patient. CONCLUSION: Our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid refractory aGVHD, particularly in the setting of intestinal involvement.

A Case of beta Thalassemia Intermedia Due to Hemoglobin Cagliari (beta 60 Val - >Glu)

Beta Thalassemia is a very rare disease in Korea. Only14 mutations have been reported in South Korea to date. This is the first case of beta thalassemia intermedia due to hemoglobin Cagliari in Korea. The locus of this missense mutation is exon 3 of beta globin (beta60 Val->Glu). This is considered a de novo mutation of dominantly inherited beta thalassemia in patients previously having no family history of this conditions. The patient showed microcytic hypochromic anemia, jaundice, and splenomegaly, which were typical characteristics of beta-thalassemia intermedia. During follow-up, there was an episode of aplastic crisis due to Parvovirus B19 infection treated with intravenous immunoglobulin. We report this case with the related literature.

Detection of nasopharyngeal carriages in children by multiplex reverse transcriptase-polymerase chain reaction / 소아과

PURPOSE: The aim of this study was to determine the prevalence of asymptomatic nasopharyngeal carriages in children using a multiplex reverse transcriptase-polymerase chain reaction (mRT-PCR) assay kit. METHODS: We obtained nasopharyngeal swabs from 33 children without any underlying disease from July 25 to July 28, 2008. The children were free from the signs of respiratory tract infections at the time of sampling. DNA was extracted from the swabs and subjected to multiplex RT-PCR using a primer set for the detection of pneumococci (Seeplex(R) PneumoBacter ACE Detection Seegene, Seoul, Korea). The amplified PCR products were separated on 2% agarose gels and stained with either ethidium bromide or screen tape system (Lab901 Scotland, UK). RESULTS: A total of 33 children (male, 15 female, 18) aged between 3.2 and 16.3 (median, 8.2) years were included in this study. The mRT-PCR detected colonized bacteria (Streptococcus pneumoniae, Hemophilus influenzae, Chlamydia pneumoniae, and Bordetella pertussis) in 30 children (90.9%). Of these, 13 children (39.4%) showed more than 2 bacteria: 12 children were positive for 2 bacteria (S. pneumoniae and H. influenzae) and 1 child was positive for 3 bacteria (S. pneumoniae, H. influenzae, and C. pneumoniae). CONCLUSION: mRT-PCR was found to be a sensitive tool for the detection of asymptomatic nasopharyngeal carriages. Clinical significances of the bacteria detected by mRT-PCR will have to be evaluated in the future.

A Case of Candida Endocarditis with Vegetation on the Tricuspid Valve in a Preterm Infnat

Fungal endocarditis is a rare disease in infants, but it has been reported with increasing frequency among premature infants requiring neonatal intensive care. Congenital heart disease, pro- longed intravenous catheterization, the use of intravenous alimentation, broad-spectrum antibiotics administration and narcotic addiction are risk factors. Candida endocarditis is an unusual but severe complication of systemic candidiasis. Its occurrence has been related to the placement of a central venous catheter with its tip close to or within the right atrium and persistent candidemia. Embolization to major blood vessels is a common complication of Candida endocarditis and repeated pulmonary emboli are suspected to be cause of the repeated episodes of circulatory shock which finally leads to death. Thus, early diagnosis of Candida invasion and prevention of Candida endocarditis are essential for survival. We report a case of Candida endocarditis which was successfully managed with surgical removal and antifungal therapy. (J Korean Pediatr Soc 2000;43:832 836)

A Case of Saldino-Noonan Type Short Rib-Polydactyly Syndrome

Short rib-polydactyly syndrome (SRPS) is a rare type of skeletal dysplasia characterized by short limb dysplasia, thoracic hypoplasia, polydactyly and multiple visceral anomalies. It is transmitted as a autosomal recessive trait. There have been 4 classic types of SRPS, of which Saldino-Noonan type is the most common, and is characterized by very narrow thorax, short limb, postaxial polydactyly, striking metaphyseal dysplasia of tubular bones, pelvic abnormalities, hypoplasia of iliac bones, flat acetabulae, and abnormalities of urogenital, anorectal and cardiovascular system. We report a newborn infant who had typical features of Saldino-Noonan type SRPS, clinically and radiologically and had compatible autopsy findings.

Caudal Regression Syndrome: A Case Report

Caudal regression syndrome is a rare congenital anomaly, which results from a developmental failure of thecaudal mesoderm during the fetal period. We present a case of caudal regression syndrome composed of a spectrum ofanomalies including sirenomelia, dysplasia of the lower lumbar vertebrae, sacrum, coccyx and pelvic bones,genitourinary and anorectal anomalies, and dysplasia of the lung, as seen during infantography and MR imaging.