OBJECTIVETo observe the effect of β₃adrenoceptors (β₃-AR) activation on rat thoracic aorta smooth muscle contractility and the possible related mechanism.

METHODSThe endothelium removed thoracic aorta was pre-contracted with 30 mmol/L KCl physiological saline solution (PSS). Then the tension of the thoracic aorta was recorded in presence of BRL37344 (BRL) to determine the action of β₃-AR. The tension of the thoracic aorta was also recorded in the presence of Propranolol (PRA), SR59230A (SR), L-NNA, H-89 and Iberiotoxin (IBTX) respectively to reveal the underling mechanism of β₃-AR activation on rat vascular smooth muscle. Immunohistochemistry was adopted to confirm the existence and the distribution of β₃-AR in rat thoracic aorta.

RESULTSThe results showed that: (1) The thoracic aorta was relaxed by β₃-AR activation, with a relaxation percentage of (10.59 ± 0.79). (2) β₃-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats. (3) PRA did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. (4) L-NNA (a NOS inhibitor) and H-89 (a PKA inhibitor) reversed the relaxation effect of BRL on vascular smooth muscle. (5) The effect of BRL was decreased after application of Ibriotoxin (IBTX), a large conductance calcium dependent potassium channel blocker.

CONCLUSIONThe results confirmed that activation of β₃-AR led to relaxation of thoracic aorta smooth muscle. The relaxation action of β₃-AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca²⁺-K⁺ channels were involved in the relaxation action of β₃-AR activation on rat thoracic aorta smooth muscle.

Animals ; Aorta, Thoracic ; physiology ; In Vitro Techniques ; Isoquinolines ; Large-Conductance Calcium-Activated Potassium Channels ; physiology ; Muscle Contraction ; Muscle Relaxation ; Muscle, Smooth, Vascular ; physiology ; Nitroarginine ; Peptides ; Propanolamines ; Propranolol ; Rats ; Receptors, Adrenergic, beta-3 ; physiology ; Signal Transduction ; Sulfonamides

Objective To investigate the efficacy and safety of rituximab in the treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods Three patients with anti-NMDAR antibodies in cerebrospinal fluid and serum hospitalized from May 2012 to July 2014 were retrospectively reviewed.The clinical syndrome,investigations,and therapeutic interventions by rituximab when first line immunotherapy failed were evaluated.Results All 3 patients were females with median age of 17 years (12,17,and 22 years).One patient had ovarian teratoma.All 3 patients presented with psychiatric symptoms and movement disorders,2 of which developed into a state of unresponsiveness.Brain magnetic resonance imaging of 2 patients was unremarkable,and 1 showed T2 and FLAIR hyperintensity among the areas of medulla,pons,caudex cerebri and callosum.Fluoro-2-deoxy-D-glucose-PET showed variable multifocal cortical and subcortical abnormalities that changed during the course of the disease.Electroencephalograms were abnormal in all patients,showing non-specific,slow,and disorganised activity,1 showing extreme delta brush.The cerebrospinal fluid showed lymphocytic pleocytosis.All patients showed no response to treatment with first line immunotherapy (corticosteroids,intravenous immunoglobulin (400 mg · kg-1 · d-1 × 5 d,2-3 courses of treatment)).After the administration of rituximab,1 patient responded slower,whereas the other 2 patients who recovered dramatically (375 mg/m2 every week for 3-4 weeks) continued immunosuppression with mycophenolatemofetil for 1 year.Relapse occurred in 1 patient when the immunotherapies discontinued 6 months later.During the treatment of rituximab,2 patients had grade 3 infectious adverse events (hospitalization and intravenous administration of antibiotics).Conclusions Rituximab is effective for the patients with anti-NMDAR encephalitis who fail to respond to the first line immunotherapy.However the utility of rituximab is still a challenge due to the risk of infectious complications and off-label use.

Objective Percheron artery is an uncommon anatomic variant. Percheron artery infarction with unilateral embryonic posterior cerebral artery ( PCA ) was rarely reported.The aim of this study was to characterize the clinical and imaging patterns of Percheron artery infarction with the unilateral embryonic PCA for early diagnosis and treatment.MethodsClinical and imaging data of 2 patients with Percheron artery infarction were reviewed retrospectively.ResultsTwo patients presented acute coma and one had paroxysmal blurred before coma.On neurological examinations,one patient had vertical gaze palsy besides two were unconsciousness. MRI showed symmetrical high signal intensity on diffusion weighed imaging (DWI)in bilateral paramedian thalami in two patients and a distinct pattern of V-shaped hyperintensity on DWI andFLAIR was present on the midbrain in one patient. Digital subtraction angiography and magnetic resonance angiography demonstrated unilateral embryonic PCA in two patients.ConclusionsThe classical clinical symptoms,symmetrical high signal in bilateral paramedian thalami and V-shaped sign in midbrain on DWI can improve recognition,evaluation and management of Percheron artery infarction.The unilateral embryonic PCA may be underlying risk factor of Percheron artery infarction.

Objective Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described brainstem-predominant inflammatory disorder responsive to steroids with characteristic magnetic resonance imaging(MRI) feature.There was no case report in China.The aim of this study was to characterize the clinical and imaging patterns of CLIPPERS for early diagnosis and treatment.Method Clinical and imaging data and therapeutic methods and following up after treatment of 1 patient diagnosed CLIPPERS were reviewed retrospectively.Results The patient presented with subacute weakness of the lower extremities,gait ataxia and facial numbness.Cerebellar ataxia and pyramidal signs were the main positive signs on neurological examinations.Brain MRI showed punctate gadolinium enhancement peppering the pons and cerebellar.Treatment with steroids led to rapid clinical improvement and marked resolution of MRI lesions which accorded with characteristics of CLIPPERS.Conclusions There are no characteristic clinical manifestations of CLIPPERS.Punctate gadolinium enhancement peppering the pons is the distinct magnetic resonance imaging feature which may suggest the clinical diagnosis of CLIPPERS.Early treatment with steroids can improve the prognosis.

The research aimed to investigate the therapeutic effects and mechanisms of Opuntia dillenii Haw polysaccharide (OPS) on atherosclerosis of rats. First atherosclerotic rat models were established by high-fat and high-calcium diet. Thirty days later, the rats were treated with low dosage of OPS (0.2 g x kg(-1) x d(-1)) or high dosage of OPS (0.4 g x kg(-1) x d(-1)) by intraperitoneal injection for 60 days continuously. At the end of treatment, thoracic aorta rings were prepared and vasorelaxation of rat thoracic aorta in different experiment groups were determined by using 620M multi wire myograph system in vitro. Blood and livers of rats were collected. Then plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) of rats were separately determined using whole automatic biochemical analyzer; protein level of hepatic apolipoprotein B (ApoB) and that of hepatic diglyceride acyltransferase (Dgat1) were measured by Western Blot technique. Results showed that the ability of rat thoracic aorta to relax decreased markedly in the model group compared with that in the normal group, and significant differences existed in vasorelaxation ratios induced by different concentrations of carbamylcholine chloride (Carb) between these two groups (P < 0.01). After OPS treatment, the ability of rat thoracic aorta to relax improved markedly, the vasorelaxation ratios induced by Carb at 5 and 10 μmol x L(-1) were respectively 0.34 ± 0.08 and 0.62 ± 0.15 in the group treated with low dosage of OPS, while the ratios induced by Carb at 1 and 5 μmol x L(-1) were respectively 0.54 ± 0.08 and 0.98 ± 0.02 in the group treated with high dosage of OPS, which were all significantly different with those in the model group (P < 0.01). Plasma contents of TC, TG and LDL reduced significantly by the treatments both with low and high dosages of OPS compared with those in the model group (P < 0.01). Protein level of hepatic ApoB and that of hepatic Dgat1 decreased significantly after the treatment with high dosage of OPS compared with those in the model group (P < 0.01). These results indicate that OPS can markedly improve the vasorelaxation of thoracic aorta of atherosclerotic rats and has significant anti-atherosclerotic effect; inhibiting the expression of ApoB and Dgat1 and thus decreasing the amounts of TC, LDL and TG serving as one of the molecular mechanisms of its antiatherosclerosis effect.
Animals ; Aorta, Thoracic ; drug effects ; Atherosclerosis ; drug therapy ; Cholesterol ; blood ; Lipoproteins, LDL ; blood ; Opuntia ; chemistry ; Phytotherapy ; Rats ; Triglycerides ; blood

BACKGROUNDThe plasma concentration of very low density lipoprotein (VLDL) is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase (MAPK) in mesangial cell proliferation induced by VLDL.

METHODSMesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by XTT assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 µmol/L PD 98059.

RESULTSTen to 500 µg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor.

CONCLUSIONThese results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.

Animals ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Lipoproteins, VLDL ; pharmacology ; Male ; Mesangial Cells ; cytology ; drug effects ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.

Microvascular decompression is an effective treatment for hemifacial spasm. Hemorrhage is oneof the complications of microvascular decompression. However, delayed hemorrhage is very rare.Here, we report a case of ipsilateral cerebellar hemorrhage at day seven following microvasculardecompression. A 45-year-old woman presented with left HFS for the previous two years. Diagnostictesting demonstrated the presence of neurosyphilis. Brain magnetic resonance image was unremarkableon presentation. She received microvascular decompression and her hemifacial spasm completelyresolved after surgery. At day seven post-operatively, the patient presented with a sudden onsetheadache. Emergency computed tomography scan showed a cerebellar hemorrhage. A suboccipitalcraniotomy was performed and a cerebellar hematoma was evacuated. The delayed hemorrhage wasattributed to possible microaneurysm from syphilis.

Metastatic brain lymphomas, which belong to secondary central nervous system lymphomas, usually originate from primary tumors of the bone marrow, testis, or orbit. Gastrointestinal lymphomas commonly metastasize to the lung or heart. We report here a case of brain hemorrhage due to metastasis from primary gastrointestinal diffuse large B-cell lymphoma (DLBCL). A 30-year-old male presented with headache. He was diagnosed to have gastrointestinal lymphoma 6 months earlier, and treated with gastrointestinal surgery. Pathological diagnosis was DLBCL. A PET-CT scan immediately after gastrointestinal surgery demonstrated no brain metastasis. On admission to the ward, imaging of the brain showed right temporoparietal hematoma. In the ward, the patient deteriorated with impaired consciousness. Repeat brain imaging showed enlargement of the hematoma. He underwent right temporoparietal craniotomy for the removal of a hematoma, and tumor nodules adherent to the cortex was found. Pathology confirmed a metastatic DLBCL in the brain. Literature review showed that this was the first reported case of brain hemorrhage from metastatic lymphoma. Metastatic central nervous system lymphoma should be considered as a differential diagnosis in patients with a history of gastrointestinal lymphoma presenting with neurological symptoms.

OBJECTIVETo analyze the therapeutic effect of human neural precursor cells transplantation in treatment of neonates with severe brain injury.

METHODThe transplantation was performed on 6 newborns, one of them was diagnosed as extremely severe carbon monoxide poisoning at 5(th) day after birth; one of them was diagnosed as severe hypoglycemia; the others had asphyxia at birth with Apgar scores from 1 to 3 and were diagnosed as severe neonatal asphyxia, severe hypoxic ischemic encephalopathy according to images, electroencephalogram, biochemical examination and clinical manifestation. With the approval of hospital ethics committee and informed consent of the family members, the newborns received human neural precursor cells transplantation at the 4(th) to 20(th) day after birth. With the agreement of a pregnant woman, forebrain cells were obtained from the forebrain of her 12-week old fetus after spontaneous abortion. The cells from the fetal brain were amplified into human neural precursor cells in vitro and were injected into the cerebral ventricle of the patients.

RESULTOn the 2(nd) day after transplantation, sucking and swallowing reflexes gradually appeared in all the patients, muscular tension was also improved, and convulsion stopped. NBNA scoring in 3 of the patients reached normal level on the 28(th) day after birth. The 6 patients were followed up for 12 months. Four patients were normal in psychomotor development and scores of each scale reached normal level. Two patients have cerebral palsy.

CONCLUSIONhNPCs transplantation is safe and effective in treatment of severe neonatal brain injury. More clinical trials and further observation are needed.

Brain Injuries ; surgery ; Female ; Humans ; Hypoxia-Ischemia, Brain ; surgery ; Infant, Newborn ; Male ; Neural Stem Cells ; cytology ; transplantation