RESUMEN
Hypoxic brain injury is accompanied by a decrease in various functions. It is also known that obstructive sleep apnea (OSA) can cause hypoxic brain injury. This study aimed to produce a model of an intermittent hypoxic brain condition in rats and determine the activity of the brain according to the duration of hypoxic exposure. Forty male Sprague-Dawley rats were divided into four groups: the control group (n = 10), the 2 h per day hypoxia exposure group (n = 10), the 4 h per day hypoxia exposure group (n = 10), and the 8 h per day hypoxia exposure group (n = 10). All rats were exposed to a hypoxic chamber containing 10% oxygen for five days. Positron emission tomography-computed tomography (PET-CT) brain images were acquired using a preclinical PET-CT scanner to evaluate the activity of brain metabolism. All the rats were subjected to normal conditions. After five days, PET-CT was performed to evaluate the recovery of brain metabolism. Western blot analysis and immunohistochemistry were performed with vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The mean SUV was elevated in the 2 h per day and 4 h per day groups, and all brain regions showed increased metabolism except the amygdala on the left side, the auditory cortex on the right side, the frontal association cortex on the right side, the parietal association cortex on the right side, and the somatosensory cortex on the right side immediately after hypoxic exposure. However, there was no difference between 5 days rest after hypoxic exposure and control group. Western blot analysis revealed the most significant immunoreactivity for VEGF in the 2, 4, and 8 h per day groups compared with the control group and quantification of VEGF immunohistochemistry showed more expression in 2 and 4 h per day groups compared with the control group. However, there was no significant difference in immunoreactivity for BDNF among the groups. The duration of exposure to hypoxia may affect the activity of the brain due to angiogenesis after intermittent hypoxic brain conditions in rats.
RESUMEN
RATIONALE: Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive trait and a rare disease characterized by abnormal myelin formation in the central nervous system. Since Pelizaeus and Merzbacher reported the pathology of PMD in the 1990s most studies have examined pharmacological treatments. No studies have reported the effects of rehabilitation on patients with PMD aimed at improving their functional abilities. We report the first case of improved development after rehabilitation in a patient with Pelizaeus-Merzbacher disease. PATIENT CONCERNS: A 1-month-boy developed focal seizures, nystagmus, and jerky head movements. He was brought to our outpatient clinic for rehabilitation of developmental delay at 11 months of age. He showed hypotonia, nystagmus, and developmental delay of 4 to 5 months in his gross and fine motor ability. DIAGNOSES: Developmental delay in a patient with PMD. INTERVENTIONS: A child with PMD was hospitalized 3 times for 3 months and underwent rehabilitation to improve developmental delay. Developmental assessments were conducted before and after each admission for rehabilitation training. OUTCOMES: Before training, the patient was unable to maintain a sitting position. After the first and second training sessions, his gross motor ability had improved, and he could sit with a mild assist. Fine motor function also improved. Before training, the patient was able to transfer a cube from one hand to the other. After training, he could perform a pincher grasp. LESSONS: Rehabilitation training can help PMD patients achieve maximal function and catch-up in their growth.
Asunto(s)
Discapacidades del Desarrollo/rehabilitación , Enfermedad de Pelizaeus-Merzbacher/rehabilitación , Humanos , Lactante , MasculinoRESUMEN
Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Compuestos Bicíclicos con Puentes/aislamiento & purificación , Compuestos Bicíclicos con Puentes/farmacología , Poríferos/química , Esteroides/aislamiento & purificación , Animales , Antiinflamatorios/química , Compuestos Bicíclicos con Puentes/química , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Biología Marina , Ratones , Estructura Molecular , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Resonancia Magnética Nuclear Biomolecular , República de Corea , Esteroides/química , Esteroides/farmacología , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
Three new sterols, 5α,8α-epidioxy-24-norcholesta-6,9(11),22-trien-3ß-ol (1), 5α,8α-epidioxy-cholesta-6,9(11),24-trien-3ß-ol (2), and 5α,8α-epidioxy-cholesta-6,23-dien-3ß,25-diol (3), with four known sterols (4-7) were isolated from a marine sponge Monanchora sp. Their chemical structures were elucidated by extensive spectroscopic analysis. Compounds 1 and 3-7 showed moderate cytotoxicity against several human carcinoma cell lines including renal (A-498), pancreatic (PANC-1 and MIA PaCa-2), and colorectal (HCT 116) cancer cell lines.
Asunto(s)
Colestadienoles/aislamiento & purificación , Colestadienoles/farmacología , Colestenos/aislamiento & purificación , Colestenos/farmacología , Noresteroides/aislamiento & purificación , Noresteroides/farmacología , Poríferos/química , Esteroles/aislamiento & purificación , Esteroles/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Esteroles/toxicidadRESUMEN
Three novel scalarane sesterterpenes were isolated from a Korean marine sponge, Psammocinia sp., along with four known derivatives. Their structures were elucidated on the basis of NMR, MS and IR spectroscopic data. The three new compounds are 12-deacetoxy-23-hydroxyscalaradial (1), 12-dehydroxy-23-hydroxyhyrtiolide (2) and 12-O-acetyl-16-deacetoxy-23-acetoxyscalarafuran (3), respectively, and the four known compounds are 12-deacetoxy-23-hydroxyheteronemin (4), 12-deacetoxy-23-acetoxy-19-O-acetylscalarin (5), 12-deacetoxy-23-O-acetoxyheteronemin (6) and 12-deacetoxyscalaradial (7). They exhibited cytotoxicity against intractable human cancer cell lines A498, ACHN, MIA-paca and PANC-1, with an IC50 range of 0.4-48 µM.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Poríferos/química , Sesterterpenos/química , Sesterterpenos/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Haplorrinos , Humanos , Células K562 , Neoplasias Renales/tratamiento farmacológico , Espectrometría de Masas , Resonancia Magnética Nuclear Biomolecular , Neoplasias Pancreáticas/tratamiento farmacológico , Sesterterpenos/aislamiento & purificación , Espectrofotometría InfrarrojaRESUMEN
Chemical investigation of a Korean marine sponge, Monanchora sp., yielded nine new sesterterpenoids (1-9) along with phorbaketals A-C (10-12). The planar structures were established on the basis of NMR and MS analysis, and the absolute configurations of 1-9 were defined using the modified Mosher's method and CD spectroscopic data analysis. Compounds 1-8, designated as phorbaketals D-K, possess a spiroketal-modified benzopyran moiety such as phorbaketal A, and their structural variations are due to oxidation and/or reduction of the tricyclic core or the side chain. Compound 9, designated as phorbin A, has a monocyclic structure and is proposed to be a possible biogenetic precursor of the phorbaketals. Compounds 1-9 were evaluated for cytotoxicity against four human cancer cell lines (A498, ACHN, MIA-paca, and PANC-1), and a few of them were found to exhibit cytotoxic activity.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Poríferos/química , Sesterterpenos/aislamiento & purificación , Sesterterpenos/farmacología , Animales , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Furanos/aislamiento & purificación , Humanos , Corea (Geográfico) , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesterterpenos/química , Compuestos de Espiro/química , Compuestos de Espiro/aislamiento & purificación , EstereoisomerismoRESUMEN
Two unprecedented phosphorus-containing iodinated polyacetylenes, phosphoiodyns A and B (1-2), were isolated from a Korean marine sponge Placospongia sp. Their structures were elucidated by spectroscopic data analysis. Phosphoiodyn A exhibited potent agonistic activity on human peroxisome proliferator-activated receptor delta (hPPARδ) with an EC(50) of 23.7 nM.
Asunto(s)
Hidrocarburos Yodados/aislamiento & purificación , Compuestos Organofosforados/aislamiento & purificación , PPAR delta/agonistas , Poliinos/aislamiento & purificación , Poríferos/química , Animales , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacología , Corea (Geográfico) , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Poliinos/química , Poliinos/farmacologíaRESUMEN
A chemical investigation of a Korean marine sponge, Phorbas sp., yielded unprecedented sesterterpenoids phorone A (1) and isophorbasone A (2) along with ansellone B (3) and phorbasone A acetate (4). Their complete structures were elucidated by the combination of spectroscopic data and chemical manipulation. Phorone A (1) and isophorbasone A (2) have the new "phorane"(5) and "isophorbasane"(6) sesterterpenoid carbon skeletons, respectively. Ansellone B (3) and phorbasone A acetate (4) exhibited potent inhibitory activity on nitric oxide production in RAW 264.7 LPS-activated mouse macrophage cells with IC(50) values of 4.5 and 2.8 µM, respectively.