الملخص
P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleTsA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO2 or minor α-and β-hydroxylated fatty acids as side-products.In this work,the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleTsA were investigated in detail by fluores-cence titration experiment,ultraviolet-visible (UV-vis) and 31p NMR spectroscopies.Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6,a repre-sentative CPHs,interacted with OleTsA with a binding constant value of 15.2 × 104 M-1 at 293 K.The thermodynamic parameters (△H,△S and △G) showed that the hydrogen bond and van der Waals force played major roles in the interaction between OleTsA and CPHs.The UV-vis and 31p NMR studies indicated the penetration of CPH-6 into the interior environment of OleTsA,which greatly affects the enzymatic activity of OleTsA.Therefore,our study revealed an effective way to use phosphorus hetero-cyclic compounds to modulate the activity of cvtochrome P450 enzymes.
الملخص
Objective To analyze the clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders(NMOSD)in children. Methods The clinical data,imaging manifestations and follow - up data of 16 NMOSD patients at Department of Pediatric Neurology,Shandong Provincial Hospital Affiliated to Shandong Univer-sity between July 2013 and September 2017 were respectively analyzed. Results In 16 patients,initial presentations included optica neuritis(ON)in 5 cases,longitudinally extensive transverse myelitis(LETM)in 6 cases,and among them there were 2 cases with acute disseminated encephalomyelitis and 3 cases with both ON and LETM. Eleven cases received aquaporin - 4(AQP4)antibody examination and 4 cases were found seropositive. One case out of 7 detected cases was found AQP4 antibody positive in cerebrospinal fluid. Eleven cases received optica magnetic resonance imaging (MRI),and 8 cases were found abnormal signals in optic nerve and optica chiasma. The spinal cord MRI showed 13 ca-ses with LETM manifestations,and abnormal signals were found in vertebral segments(5 - 13),and among them 1 case had cervical cord,3 cases were thoracic cord and 9 cases were both of the above. Lesions in the cervical cord in 2 cases were extended upward to the medulla. Fifteen cases received brain MRI and all of them had brain lesions,which were mainly involved in the central and subcortical white matter,thalamus,corpus callosum,brainstem,the junction of spinal cord and medulla,cerebellum,and so on. All patients received treatment for acute attacks with high - dose Methylpred-nisolone and/ or gamma globulin and got obvious relief. Two cases with recurrent ON received treatment of Rituximab and their vision became improved. Fifteen patients were followed up,and 2 cases had limb disorders and 4 cases had visual impairment,other patients had no clinical symptoms. Conclusions Pediatric NMOSD has a diverse clinical pre-sentation at the onset disease. Those who are initial diagnosed acute myelitis,ON and acute disseminated encephalomye-litis should be considered the possibility of NMOSD. Antibody to AQP4 testing can assist the diagnosis. The typical ima-ging characters of NMOSD children are abnormal signals in the high expression area of AQP4. Intracranial lesions are more common in children. The acute treatment includes the high - dose Methylprednisolone and gamma globulin. Rituximab can be used for the recurrent patients.
الملخص
Objective To investigate the effect of Propranolol and Phentolamine on neurogenic pulmonary ede-ma(NPE)in rats. Methods One hundred and twenty male Wistar rats were randomly divided into 4 groups:the con-trol group(group A),the NPE group(group B),the Propranolol treatment group(group C)and the Phentolamine treatment group(group D),30 cases in each group. Diffuse brain injury was induced in the latter 3 groups. The lung wet/ dry ratio was calculated. HE staining was used to measure the histological changes in the lung tissues. The levels of neuropeptide Y(NPY)and substance P(SP)in the serum and the bronchoalveolar lavage fluid(BALF)were detected by enzyme - linked immunosorbent assay(ELISA). The expressions of NPY and SP in the lung tissues were demonstra-ted by immunohistochemical staining,and immunohistochemical scores(IHS)were measured after scarifying the ani-mals at different time points(0. 5,6. 0 and 24. 0 h after injury). Results Compared with group A,water volume in the lungs in group B increased at 24. 0 h(P ﹤ 0. 05);NPY content in the serum was elevated at 6. 0 h,while that in BALF was elevated at 6. 0 h and 24. 0 h(all P ﹤ 0. 05);SP content in the serum was elevated at 0. 5 h and 6. 0 h(all P ﹤0. 05),while that in BALF was elevated at 0. 5 h(P ﹤ 0. 05);The expression of NPY protein in the lung tissue in-creased at 0. 5 h,6. 0 h and 24. 0 h(all P ﹤ 0. 05),while the level of SP protein increased at 0. 5 h(P ﹤ 0. 05). Com-pared with group B,water volume in the lungs in group C was higher at 6. 0 h and 24. 0 h(all P ﹤ 0. 05);NPY concen-trations in the serum were higher at 6. 0 h and 24. 0 h(all P ﹤ 0. 05),while those in BALF were higher at 0. 5 h, 6. 0 h,and 24. 0 h(all P ﹤ 0. 05);SP concentrations in serum and BALF were higher at 0. 5 h(all P ﹤ 0. 05). The ex-pression of NPY protein increased at 6. 0 h(P ﹤ 0. 05),while the levels of SP protein increased at 0. 5 h,6. 0 h and 24. 0 h(all P ﹤ 0. 05). Compared with group B,the level of NPY in serum in group D was lower at 6. 0 h,and that in BALF was lower at 6. 0 h and 24. 0 h(all P ﹤ 0. 05). The level of SP in serum was lower at 0. 5 h(P ﹤ 0. 05). The ex-pression of NPY protein decreased at 6. 0 h and 24. 0 h(all P ﹤ 0. 05),while the levels of SP protein decreased at 0. 5 h(P ﹤ 0. 05). Conclusions Phentolamine is effective in reducing NPE through reduction of NPY and SP,while propranolol can stimulate the release of NPY and SP to aggravate NPE following traumatic brain injury in rats.