Objectives To investigate the relationship of sex difference with serum bisphenol-A (BP-A),adiponectin and metabolic syndrome (MetS)in elderly patients with isolated systolic hypertension(EISH).Methods A retrospective study of the clinical data was conducted in 540 subjects from the Cardiology and Geriatric Department in the Affiliated Hospital of Shanxi Medical University,Changzhi Municipal People,s Hospital and the Department of Cardiology of Shanxi Medical University,First Clinic Hospital from January 2010 to December 2013.Elderly patients with EISH were divided into male group(n=270)and female group(n=270).Meanwhile 560 older health persons were severed as controls,including 300 females and 260 males.The changes of BP-A and adiponectin (Ad) concentration were measured.The blood lipid,insulin resistance index (HOMA-IR),blood pressure,body mass index,heart rate variability and ultrasonic change of heart and blood vessel were tested regularly.Results The level of serum BP-A[(0.89±0.10)ng/L vs.(0.57±0.04)ng/L]and [(0.64±0.10)ng/L vs.(0.55 ± 0.08)ng/L] were higher in male EISH vs in male control,and in female EISH than in female control (F =23.76,23.86,all P ＜ 0.01),respectively.The levels of adiponectin were lower in male EISH vs control[(4.9±1.4)ng/L vs.(10.5±2.7)ng/L and in female EISH vs control(6.0±1.3) ng/L vs.(11.5±3.3)ng/L),F=13.10,16.20,all P＜0.01.Root mean sequare of the successive normal sinus RR interval difference(rMSSD)were lower in male/ female EISH than control groups(F=13.10、13.70,P ＜0.01).Serum BP-A level was positively correlated with the bocly mass index and systolic pressure (r =0.38,0.54,P ＜ 0.01),and was negatively correlated with serum Ad and rMSSD(r=-0.46,-0.42,P＜0.01).Conclusions Obvious gender difference in changes of serum BP-A exists in older patients with EISH.Network cytokines may take part in the pathophysiological process of the obesity related hypertension.

Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.
Acute Disease ; Brain Diseases ; etiology ; Child ; Humans ; Magnetic Resonance Imaging ; Male ; Maple Syrup Urine Disease ; complications ; diagnosis ; therapy

Objective To observe the clinical efficacy of transplantation with autologous bone marrow mesenchymal stem cells (MSCs) in the treatment of children with severe mental retardation (MR). Methods Fifty children with severe MR (2-6 years old), admitted to our hospital from May 2008 to December 2009, were chosen; self-control observation on the mental and motor developments of these children in the same length of time periods was performed 6 months before and 6 months after the autologous bone marrow MSCs transplantation. Meanwhile, the improvements of each patient were followed up and analyzed 1, 3 and 6 months after the transplantation. Results Two patients failed in the culture of bone marrow MSCs; 6 patients failed in follow-up; the other 42 were observed completely.Significant improvement was noted in 25 patients after the transplantation with an effective rate reaching 59.5%; gradual mental and motor improvements appeared in these 25 patients 1 month after the transplantation, and lasted till the 6th month of transplantation. The average scores of mental improvement were (4.67±4.20) in 6 months before transplantation, and (17.12±13.05) in 6 months after transplantation (t=6.816, P=0.000). The average times having gross motor improvement 6 months before and 6 months after transplantation were (1.019±0.78) and (1.15±0.91), respectively (t=1.610, P＞0.05); the average times having fine motor improvement were (0.89±0.79) and (3.40±3.16) months in 6 months before and 6months after transplantation (t=5.030, P＜0.05); the average times having language improvement were (0.99±0.95) and (3.23±3.30) months in 6 months before and 6 months after transplantation (t=4.000, P＜0.05); the average times having personal-social behavior progress were (1.03±0.81) and (2.95±3.68)months in 6 months before and 6 months after transplantation (t=3.509, P＜0.05); the average times having adaptive behavior progress were (0.88±1.22) and (1.19±1.48) months in 6 months before and 6 months after transplantation (t=1.322, P＞0.05). Conclusion Autologous bone marrow MSCs transplantation can improve the intellectual development in a short time, mainly in the fine motor, language and personal-social behavior, in children with severe MR. Bone marrow MSCs transplantation for severe MR is safe and effective in a short-term.

OBJECTIVETo observe the alteration of interleukin-17 and interferon-γ double positive cells (IL-17(+)/IFN-γ(+) cells) in mice with coxsackie virus B3 (CVB3) induced acute viral myocarditis (VMC).

METHODSVMC was induced in male Balb/c mice by peritoneal injection of CVB3. Control mice received PBS injection. At 0, 1, 2, 3, 4 and 6 weeks after injection, pathological scores were determined on hematoxylin-eosin stained heart sections and flow cytometric analysis was performed to evaluate the percent of IL-17(+)/IFN-γ(+) cells among CD4(+) T cells.

RESULTSCompared to control mice, the pathological scores of VMC mice were higher on CVB3 infection week 1 (1.8 ± 0.5), peaked on week 2 (2.8 ± 0.5) and declined thereafter. However, the proportion of IL-17(+)/IFN-γ(+) cells remained steadily at a low level throughout the observation period and was similar between VMC and control mice.

CONCLUSIONSOur data shows that IL-17(+)/IFN-γ(+) cells might not be involved in the inflammation process of CVB3 induced VMC mice model.

Animals ; Coxsackievirus Infections ; immunology ; pathology ; Disease Models, Animal ; Enterovirus ; Interferon-gamma ; metabolism ; Interleukin-17 ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; immunology ; pathology ; virology ; Myocardium ; pathology ; Th17 Cells ; immunology ; metabolism

Blood Cell Count ; Bone Marrow Cells ; metabolism ; Child ; Cord Blood Stem Cell Transplantation ; Cytokines ; therapeutic use ; Histocompatibility Testing ; Humans ; Male ; Myelodysplastic Syndromes ; blood ; therapy ; Treatment Outcome

OBJECTIVESevere newborn hypoxic-ischemic encephalopathy (HIE) has a very high rate of disability and no effective treatment is available. The present study aimed to preliminarily evaluate the effects of human neural stem cell transplantation in treatment of severe neonatal HIE.

METHODSThe patient was a 75-day old male infant with sequelae of severe HIE who had highly delayed development of intelligence and movement and myotonia. MRI showed multiple cerebromalacia and encephalatrophy. Cells obtained from the forebrain of an 11-week old fetus were cultured and amplified for 15 days. And then the human fetal neural stem cells were injected into cerebral ventricle of this infant.

RESULTSTwenty eight days after transplantation, remarkable improvement occurred not only in his myotonia but also in his intelligence and movement, which became similar to those of the normal infants of the same age. Positron emission tomography (PET) showed significantly increased radioactivity at temporal and occipital lobes which suggested that the cellular metabolism had increased greatly.

CONCLUSIONThe short-term effect of NSCs transplantation on the infant with severe HIE sequelae was significant. PET suggested that the implanted NSCs survived. Many more studies are needed to evaluate long-term effects of NSC transplantation in treatment of HIE.

Asphyxia Neonatorum ; complications ; Brain ; pathology ; physiopathology ; Female ; Humans ; Hypoxia-Ischemia, Brain ; etiology ; pathology ; physiopathology ; therapy ; Infant ; Infant, Newborn ; Injections, Intraventricular ; Multipotent Stem Cells ; transplantation ; Neurons ; Positron-Emission Tomography ; Prognosis ; Stem Cell Transplantation ; methods ; Time Factors ; Treatment Outcome

OBJECTIVENeonatal hypoxic-ischemic encephalopathy (HIE) harms the lives and health of newborn infants and children severely. Given the absence of effective therapies for HIE, it is important to derive new strategies. Neural stem cells (NSCs) have great potential as a therapeutic tool for the repair of a number of central nervous system disorders that involve cell loss. This study was designed to transplant the neural stem cells derived from human fetal brain (hNSCs) into cerebral ventricle of neonatal rat following hypoxic-ischemic injury and to investigate their survival, migration and differentiation in rat brain.

METHODSCells obtained from the forebrain of a 12-week old fetus were cultured in the presence of epidermal growth factor, basic fibroblast growth factor and leukemia inhibitory factor for 11 days. Animal models were built in 7-day-postnatal Wistar rats, 3-days after hypoxia-ischemia (HI), 5 microl suspension containing 5.0 x 10(5) hNSCs was injected into the left cerebral ventricle of each HIE rat by using stereotactic instrument. No immunosuppression therapy was given to the animals. At 1, 2, 4 weeks and 3 months after transplantation, the rats were sacrificed and brain tissues were harvested and were then examined by H-E staining and immunohistochemical analysis.

RESULTSImplanted cells expressing human nuclear protein (hNP) migrated form the subventricular zone (SVZ) along corpus callosum to the damaged areas, especially to the injured side of cortex and hippocampus. In different areas, the implanted hNSCs differentiated into different cell types which were similar to the host cells. The 85% implanted cells in cortex consisted of hNuc-NF or hNuc-Tublin double positive cells, while in the migratory way, 60% implanted cells differentiated into hNuc-GFAP double positive cells. Compared with the 1-week time point, an increased number of hNP-positive cells were observed at 2-weeks, but the number of these cells greatly decreased at 4-weeks and 3 months.

CONCLUSIONThe implanted hNSCs could extensively survive, migrate in the brain of neonatal rat with HIE and could differentiate into neurons and astrocytes in a regionally specific manner.

Animals ; Animals, Newborn ; Brain ; pathology ; Carotid Artery, Common ; surgery ; Cell Differentiation ; Cell Movement ; Disease Models, Animal ; Fetal Stem Cells ; transplantation ; Humans ; Hypoxia ; complications ; physiopathology ; Hypoxia-Ischemia, Brain ; pathology ; physiopathology ; therapy ; Immunohistochemistry ; Injections, Intraventricular ; methods ; Ligation ; methods ; Neurons ; Nuclear Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation ; methods ; Survival Analysis ; Time Factors

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

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.
AC133 Antigen ; Ammonia ; blood ; Antigens, CD ; analysis ; Arginine ; blood ; Citrulline ; blood ; Female ; Glycoproteins ; analysis ; Hepatic Artery ; Humans ; Hyperammonemia ; blood ; surgery ; Infant ; Male ; Peptides ; analysis ; Stem Cell Transplantation

OBJECTIVETo assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.

METHODSTwenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later.

RESULTSNo delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05).

CONCLUSIONSThese results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.

Child ; Child Development Disorders, Pervasive ; therapy ; Child, Preschool ; Female ; Humans ; Male ; Neural Stem Cells ; transplantation ; Rett Syndrome ; therapy