Polyphenolic Biflavonoids Inhibit Amyloid-Beta Fibrillation and Disaggregate Preformed Amyloid-Beta Fibrils

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals world-wide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an in vitro thioflavin T assay with Aβ1–42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1–40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1–42 fibrillization (IC50: 0.26 μM), as well as on disassembling preformed Aβ1–42 fibrils (EC50: 0.59 μM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1–42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1–42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1–42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1–42 fibrillization and disaggregation of preformed mature Aβ1–42 fibrils.

Clinical Significance of Neonatal Lenticulostriate Vasculopathy: Association with Congenital Cytomegalovirus Infection

PURPOSE: To investigate clinical characteristics of neonates with lenticulostriate vasculopathy (LSV) and determine the correlation between LSV and clinical characteristics, especially congenital cytomegalovirus (CMV) infection. METHODS: We retrospectively reviewed the medical records of neonates with LSV, born at Cheil General Hospital between January 2005 and December 2015. LSV was graded into three groups based on the number of the LSV lesions and classified into an isolated and combined group showing LSV with coexistent abnormalities noted on brain sonography. We compared clinical data based on the LSV classification. RESULTS: Our study included 102 neonates with LSV, which showed an unilateral pattern in 10 and bilateral pattern in 92 neonates. The numbers of neonates studied based on LSV grading were 33, 53, and 16 in grade 1, 2, and 3, respectively. We observed the isolated LSV in 62 and the combined type in 40 neonates. We observed that 93 (91.2%) of the neonates with LSV did not show specific underlying cause for this condition. Congenital CMV infection was detected in 7 neonates, including 0, 5, and 2 neonates belonging to grade 1, 2, and 3, respectively. Among these, 2 neonates showed the isolated, and 5 showed the combined type of LSV. Statistically, congenital CMV infection was more significantly associated with LSV in grade 2 and 3 than in grade 1 (P < 0.05). Additionally, congenital CMV infection was more commonly observed in the combined than in the isolated LSV type showing a marginal association (P=0.07). CONCLUSION: We observed that LSV was not clinically significant except when associated with CMV infection. We suggest that neonates presenting with a grade 2 or higher of LSV or a combined type of LSV detected via neonatal brain ultrasonography should be evaluated for CMV infection.

Development of an Ex Vivo Model for the Study of Cerebrovascular Function Utilizing Isolated Mouse Olfactory Artery

OBJECTIVE: Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. METHODS: The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately -500 microm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). RESULTS: We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH2. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. CONCLUSION: Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

A Clinical Study of Congenital Intrahepatic Portosystemic Shunt Diagnosed in Neonatal Period

PURPOSE: Congenital intrahepatic portosystemic shunts are rare disease and clinically asymptomatic shunts may be detected by chance on ultrasonogram before and after birth. We studied clinical course, treatment and prognosis of congenital intrahepatic portosystemic shunt at prenatal or neonatal period. METHODS: Medical records of 8 patients which were diagnosed in intrahepatic portosystemic shunt in Cheil General Hospital from 2006 through 2010 were reviewed retrospectively. RESULTS: Eight patients with congenital intrahepatic portosystemic shunts were identified. Six patients were diagnosed at prenatal radiological screening, including three cases of intrauterine growth restriction and two cases of preterm baby. One case with increased serum ammonia underwent coil embolization. In four cases including one case that presented elevated direct bilirubin, shunts were closed spontaneously within 11th month after birth. Two patients were diagnosed on abdominal sonogram after birth because of elevated direct hyperbilirubinemia, all of whom presented intrauterine growth restriction. Closure of shunts was confirmed during 4th month to 6th month. CONCLUSION: Congenital intrahepatic portosystemic shunts are clinically asymptomatic mostly and spontaneous closure is expected within 2 years age. But occasionally they have severe complication, so clinical and radiological observation is needed. Specially in cases of intrauterine growth retardation without evident cause, the possible diagnosis of congenital intrahepatic portosystemic shunts should be considered and prenatal and postnatal examination should be performed. When prenatal diagnosis is made, fetal wellbeing should be monitored periodically until spontaneous closure of shunts.

Fetal Intraabdominal Calcifications: Prenatal and Postnatal Course / 대한주산의학회잡지

PURPOSE: Recently, with the improvement of techniques for antenatal ultrasonography, fetal intraabdominal calcifications have been increasingly detected. These findings are important because they can signify meconium peritonitis, intrauterine infection, or thromboembolism in hepatic or portal vein. So, we studied clinical course of fetuses and infants with intraabdominal calcifications prenatally and postnatally. METHODS: We analyzed retrospectively medical records of 47 mothers and their 38 children diagnosed with fetal intraabdominal calcifications at Cheil General Hospital & Women's Health Care Center, Kwandong University College of Medicine from January 2003 to December 2008. Fetal intraabdominal calcifications were divided into the two groups, 'extrahepatic-intraabdominal calcifications' and 'hepatic calcifications', and assorted again into 'simple type' and 'complicated type' respectively. And their clinical course and outcome were compared. RESULTS: Among 47 pregnant women with intraabdominal calcifications, 31 fetuses were suspected of meconium peritonitis, 12 revealed hepatic calcifications, and 4 had other calcifications. Seven pregnant women had lost to follow up, while 2 were intrauterine fetal demise and artificial termination of pregnancy, respectively. Thirty-eight babies were born and postnatal ultrasonography was done for 31 cases. The group of meconium peritonitis was divided into simple type (64.5%) and complicated type (35.5%). Among them, surgical treatments were needed for 2 infants, one had simple type and the other had complicated meconium peritonitis, respectively. The group of hepatic calcifications was divided into simple type (75%) and complicated type (25%). None of them needed any treatment and they showed good clinical course. CONCLUSION: Fetal intraabdominal calcifications are relatively frequent and benign disease with good clinical outcome. However, because of need for neonatal surgery, periodic and steady follow-up by ultrasonography is needed prenatally and postnatally.

Clinical characteristics and courses of congenital muscular torticollis / 소아과

PURPOSE: Congenital muscular torticollis (CMT), a common musculoskeletal disorder in infants, is characterized by the rotation and flexion deformity of the neck caused by sternocleidomastoid muscle shortening. We investigated the clinical courses and perinatal risk factors of CMT. METHODS: Less than 6-month-old patients (98; M:F = 60:38) diagnosed with CMT between February 2007 and August 2008 were classified into 2 clinical subgroups, namely, SMT (sternocleidomastoid tumor) and POST (postural torticollis). All the patients were physically and neurologically examined prospectively and their cervical X-rays and ultrasonographies were obtained. Their medical histories about perinatal problems were recorded. Of the 98 patients, 45 with normal range of motion were taught passive physical exercises and 43 were referred to the Department of Rehabilitation for undergoing manual stretching therapy. RESULTS: The mean age at initial assessment was 2.2 months (SMT: 1.4+/-1.0, POST: 2.7+/-1.6). SMT presented earlier than POST. All ophthalmologic examinations and cervical X-rays were normal. SMT was associated with higher incidence of caput succedaneum and cephalhematoma. POST was highly associated with plagiocephaly. Mean duration of rehabilitative physical therapy was 3.7 months (SMT: 4.6+/-2.5, POST: 2.6+/-1.9). POST resolved earlier than SMT. Of the 88 patients with follow-up, 87 had total resolution and only 1 had residual torticollis. CONCLUSION: All the patients received early treatment with passive stretching exercises. CMT was associated with perinatal problems and had various risk factors such as obstetrical problems.

Clinical characteristics and courses of congenital muscular torticollis / 소아과

PURPOSE: Congenital muscular torticollis (CMT), a common musculoskeletal disorder in infants, is characterized by the rotation and flexion deformity of the neck caused by sternocleidomastoid muscle shortening. We investigated the clinical courses and perinatal risk factors of CMT. METHODS: Less than 6-month-old patients (98; M:F = 60:38) diagnosed with CMT between February 2007 and August 2008 were classified into 2 clinical subgroups, namely, SMT (sternocleidomastoid tumor) and POST (postural torticollis). All the patients were physically and neurologically examined prospectively and their cervical X-rays and ultrasonographies were obtained. Their medical histories about perinatal problems were recorded. Of the 98 patients, 45 with normal range of motion were taught passive physical exercises and 43 were referred to the Department of Rehabilitation for undergoing manual stretching therapy. RESULTS: The mean age at initial assessment was 2.2 months (SMT: 1.4+/-1.0, POST: 2.7+/-1.6). SMT presented earlier than POST. All ophthalmologic examinations and cervical X-rays were normal. SMT was associated with higher incidence of caput succedaneum and cephalhematoma. POST was highly associated with plagiocephaly. Mean duration of rehabilitative physical therapy was 3.7 months (SMT: 4.6+/-2.5, POST: 2.6+/-1.9). POST resolved earlier than SMT. Of the 88 patients with follow-up, 87 had total resolution and only 1 had residual torticollis. CONCLUSION: All the patients received early treatment with passive stretching exercises. CMT was associated with perinatal problems and had various risk factors such as obstetrical problems.

Characteristics and Clinical Course of Ovarian Hernias in Infants

PURPOSE: Inguinal hernias are common in children and sometimes are associated with dangerous complications, such as incarceration. There are no established management guidelines for ovarian hernias. We have reviewed the clinical course of ovarian hernias in infants. METHODS: We reviewed the medical records of female infants diagnosed with ovarian hernias by ultrasonogram at Kwandong University College of Medicine, Cheil General Hospital, and the Women's Healthcare Center between March 2001 and August 2007. We analyzed the patients gestational age, birth weight, age at the time of detection of the inguinal mass, the patients chief complaints, operative time, post-operative complications, and ultrasonographic findings. RESULTS: Eight female infants had ovarian hernias, four of whom were born prematurely. Seven infants had left-sided ovarian hernias, and one infant had a right-sided ovarian hernia. Five infants underwent surgery and there were no postoperative complications or recurrences. Three girls did not have surgery, and the ovarian hernias regressed spontaneously, with no recurrences or complications. The regression time of inguinal masses ranged from 70-161 days after birth. CONCLUSION: Physical examination to detect movable masses within the labium major in premature female infants is important because the incidence of premature inguinal hernias is much higher than in term infants. No rational medical treatment plans for female ovarian hernias have been published to date. We cared for three girls with spontaneous regression of ovarian hernias. Pediatricians should be aware whether emergent surgery for ovarian hernias is indicated.

A Symptom-free Congenital Sliding Hiatal Hernia Diagnosed within 24 Hours after Birth

The classification of hiatal hernia is made by the position of the gastroesophageal junction. Although sliding hiatal hernia (type 1) is the most common type of hiatal hernia, it is very uncommon to be found in early infancy because it is usually symptom free. We report a case of type 1 hiatal hernia of newborn infant who had diagnosed by simple chest radiography taken because of transient tachypnea of the newborn.