Objective To define the effect and mechanism of hyperkalemic solution on atrial natriuretic peptide (ANP) secretion in rabbits. Methods Eighteen rabbits were selected and the chest was opened under anes-thetization to remove the heart. The left atrium was isolated and fixed in the atrial perfusion system with proper electric stimulation for beating. The following experiments were carried out on beating rabbit atria: ①The atrium was perfused for 60 min to stabilize parameters of ANP secretion and atrial dynamics. The control period (12 min as an experimental cycle) was followed by an infusion of hyperkalemic solution (K+ concentration of hyperkalemic solution was 5.64 mmol/L and the osmolarity of hyperkalemic solution was unchanged) for three cycles, then normal K+ cancentration was recovered for two cycles;②The control period was followed by an infusion of L type Ca2+ channel blocker nifedipine (1.0 μmol/L) for three cycles;③L type Ca2+ channel inhibitor nifedipine (1.0 μmol/L) was infused for 36 rain prior (three cycles) to infusion of hyperkalemic solution. Atrial stroke volume was determined and the ANP secretion was measured by radioimmtmoaasay. Results (1)Hyperkalemic solution increased atrial ANP secretion (P<0.01) and reduced the atrial stroke volume,hut the difference was not statistically significant as compared with that of the control cycle(P>0.05). The recovery trend was to the normal level of ANP secretion and atrial stroke volume was to become normal gradually when solution level recovered to normal ,which was not significantly different from that of the control cycle (P>0.05) ;②Nifedipine (1.0 μmol/L) also increased the atrial ANP secretion (P<0.01 or P <0.05) while decreasing atrial stroke volume (P<0.01 or P < 0.05 ) ; ③Nifodipine (1.0μmol/L) completely blocked the effect of hyperkalemic solution so to increase the ANP secretion (P <0.01 ). Conclusion Hyperkalemic solution significantly increases atrial ANP secretion via extracellular high K+ competitive inhibition of extracellular Ca2+ inflow in beating rabbit atria.

Creatine Kinase ; Humans

OBJECTIVETo evaluate the therapeutic effect of percutaneous vertebroplasty (PVP) guided by X-ray fluoroscopy in treating osteoporotic spinal compression fractures, hemangioma of vertebra and metastatic carcinoma of vertebra.

METHODSOne hundred and ninety patients with 275 diseased vertebra underwent PVP under the guidance of C-arm fluoroscopy (male 80, female 110, ranging in age from 53 to 91 years, with an average of 66 years). Bone marrow biopsy needle was inserted percutaneously via transpedicular way into the diseased vertebra. Polymethylmethacrylate (PMMA) was then injected into the diseased vertebra. Visual analogue scale (VAS), mobility and analgesic usage were evaluated pre-operation and 3 months after PVP.

RESULTSPVP was successful in 190 cases (275 vertebrae). VAS was tested by t test at 3 months after PVP (P < 0.05). Simultaneously, scale of patient's mobility and scale of analgesic usage was tested by rank sum test at 3 months after PVP (P < 0.05).

CONCLUSIONAs the mimimally invasive operation, PVP can alleviate pain in early time, avoid kinds of complications by shortening the patient's time in bed and have the characteristic of simply operative procedure and low expenses. It is an effective mini-invasive technique for osteoporotic spinal compression fractures, hemangioma of vertebra and metastatic carcinoma of vertebra.

Aged ; Aged, 80 and over ; Female ; Fluoroscopy ; Fractures, Compression ; surgery ; Humans ; Male ; Middle Aged ; Osteoporosis ; complications ; Polymethyl Methacrylate ; Postoperative Complications ; prevention & control ; Spinal Fractures ; surgery ; Spinal Neoplasms ; surgery ; Vertebroplasty ; adverse effects ; methods

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na(+)-K(+)-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 micromol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 micromol/L), an inhibitor for reverse mode of Na(+)-Ca(2+) exchangers (NCX), but did not by L-type Ca2+ channel blocker nifedipine (1.0 micromol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 micromol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 micromol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 micromol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 micromol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.
8-Bromo Cyclic Adenosine Monophosphate ; Adenosine ; Cardiomegaly ; Colforsin ; Cyclic AMP-Dependent Protein Kinases ; Endothelin-1* ; Heart Diseases ; Nifedipine ; Ouabain* ; Phosphotransferases ; Protein Kinases

BACKGROUNDThere are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.

METHODSThe right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.

RESULTSGrafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded.

CONCLUSIONCultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

Animals ; Astrocytes ; transplantation ; Brain ; pathology ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Cerebral Infarction ; metabolism ; pathology ; therapy ; Fetal Tissue Transplantation ; Glial Fibrillary Acidic Protein ; analysis ; Humans ; Microtubule-Associated Proteins ; analysis ; Neocortex ; cytology ; Neurons ; transplantation ; Rats ; Synaptophysin ; analysis

BACKGROUNDAutoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor (GABA B R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement.

METHODSSerum and cerebrospinal fluid (CSF) samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABA B R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed.

RESULTSAll eighteen anti-GABA B R antibody-positive cases had limbic syndromes, and electroencephalogram (EEG) or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen (17/18) patients presented with new-onset refractory seizure or status epileptics. Twelve (12/18) patients had memory deficits, 11 (11/18) patients had personality change, 7 (7/18) patients had disturbance of consciousness, and 3 (3/18) patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 (6/18) patients. Ten (10/18) patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten (10/18) patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications.

CONCLUSIONSOur study demonstrates that most Han Chinese patients with anti-GABA B R antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABA B R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

Adult ; Autoantibodies ; immunology ; China ; Electroencephalography ; Epilepsy ; immunology ; pathology ; Female ; Humans ; Limbic Encephalitis ; immunology ; pathology ; Male ; Middle Aged ; Receptors, N-Methyl-D-Aspartate ; immunology ; Retrospective Studies ; gamma-Aminobutyric Acid ; metabolism

BACKGROUNDThe new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to address the systematic underestimation of glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with relatively well-preserved kidney function. Performance of the new equation in the Chinese population is unknown. The goal of the present study was to compare performance of these two equations in Chinese patients with chronic kidney disease (CKD).

METHODSWe enrolled 450 Chinese patients (239 women and 211 men) with CKD in the present study. The renal dynamic imaging method was used to measure the referenced standard GFR (rGFR) for comparison with estimations using the two equations. Their overall performance was assessed with the Bland-Altman method and receiver-operating characteristics (ROC) analysis. Performance of the two equations in lower and higher estimated GFR (eGFR) subgroups was further investigated.

RESULTSBoth eGFRs correlated well with rGFR (r = 0.88, 0.81, P < 0.05). In overall performance, the CKD-EPI equation showed less bias, higher precision and improved accuracy, and was better for detecting CKD. In the higher-eGFR subgroup, the CKD-EPI equation corrected the underestimation of GFR by the abbreviated MDRD equation.

CONCLUSIONSThe CKD-EPI equation outperformed the abbreviated MDRD equation not only in overall performance but also in the subgroups studied. For the present, the CKD-EPI equation appears to be the first-choice prediction equation for estimating GFR.

Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Kidney Failure, Chronic ; physiopathology ; Male ; Middle Aged ; Models, Theoretical

OBJECTIVETo study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS).

METHODSOne hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants.

RESULTSThe incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05).

CONCLUSIONSTrace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.

Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glomerular Mesangium ; immunology ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulin M ; analysis ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Nephrosis, Lipoid ; drug therapy ; immunology ; Retrospective Studies