BACKGROUNDPDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart.

METHODSWe employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting.

RESULTSPDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts.

CONCLUSIONOur results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.

3-Phosphoinositide-Dependent Protein Kinases ; Adult ; Animals ; Female ; Glycogen Synthase Kinase 3 ; physiology ; Heart ; physiology ; Heart Failure ; enzymology ; etiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Myosin Heavy Chains ; physiology ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; Tamoxifen ; pharmacology

OBJECTIVETo investigate the clinical presentation, diagnosis, treatment and outcome of patients with pulmonary veno-occlusive disease (PVOD).

METHODSData from patients diagnosed as PVOD from May 2008 to May 2011 in Shanghai Pulmonary Hospital, Tongji University were retrospectively reviewed.

RESULTSDuring this period, 5 patients [4 female, aged from 12 to 42 (22 ± 12) years old] were diagnosed as PVOD. The durations from symptoms onset to PVOD diagnosis was 2 to 50 (16 ± 20) months and four of them were previously diagnosed as idiopathic pulmonary arterial hypertension. All patients at the time of PVOD diagnosis had a severely impaired WHO pulmonary hypertension functional class (3 in class III and 2 in class IV). Furthermore, all patients characterized by a typical sign of centrilobular ground-glass opacities in high-resolution computed tomography, a markedly reduction of diffusing capacity of the lung for carbon monoxide [(38 ± 12)% of predicted value] in pulmonary functional test and severely compromised cardio-pulmonary hemodynamics identified by right heart catheterization. All patients received conventional and pulmonary arterial hypertension specific therapies, and then followed-up regularly. Up to now, 4 out of 5 patients died due to refractory right heart failure. The durations from symptoms onset to death and from PVOD establish to death were 5 - 65 (27 ± 26) months and 1 - 16 (9 ± 9) months, respectively.

CONCLUSIONSPVOD is a rare and malignant cardio-pulmonary disorder that often be misdiagnosed as idiopathic pulmonary arterial hypertension. Given the poor responses to modern pulmonary arterial hypertension specific therapies, lung transplantation remains the treatment of choice.

Adolescent ; Adult ; Cardiac Catheterization ; China ; Diagnostic Errors ; Familial Primary Pulmonary Hypertension ; pathology ; therapy ; Female ; Hemodynamics ; Humans ; Lung ; Lung Transplantation ; Male ; Pulmonary Veno-Occlusive Disease ; diagnosis ; pathology ; therapy ; Retrospective Studies ; Tomography, X-Ray Computed ; Young Adult

BACKGROUNDStem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated.

METHODSMesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with (99m)Tc. Cardiomyopathy model was induced by doxorubicin in rats. (99m)Tc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry, mRNA and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured.

RESULTSLabeling efficiency of mesenchymal stem cells was (70.0 ± 11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both mRNA and protein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts.

CONCLUSIONIn dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1 in heart may induce mesenchymal stem cells home to the heart.

Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cardiomyopathy, Dilated ; therapy ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; metabolism ; Immunohistochemistry ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To explore the characteristics of unmet needs and services of rehabilitation for people with physical disabilities (PWPs). Methods:A total of 1 512 438 PWPs administration data of unmet needs and services of rehabilitation at provincial level were sampled and analyzed the characteristics of needs and services of rehabilitation, and the related factors of needs and services. Results:The reported unmet needs of PWPs from high to low were assistive devices assistive devices (55.9%), nursing care (27.0%), medicine (26.3%), functional training (23.9%) and surgery (2.3%). Received service of rehabilitation. The services of rehabilitation for PWPs arranged as assistive devices (48.2%), nursing caring (26.4%), functional training (24.3%), medicine (19.5%) and surgery (1.4%). The logistic regression model showed that age and severity of disabilities had significant effect on the reported unmet needs of rehabilitation and received services for PWPs (P < 0.001). Conclusion:PWPs reported unmet needs mainly in the fields of assistive devices, nursing care, medicine and rehabilitation training. They received primary services included assistive devices, nursing care and rehabilitation training and therapies. The services development will emphasize the accessibility and coverage. According to ICF model, it proposed to take measures to implement individualized and precise rehabilitation services to improve the quality of services.