BACKGROUNDStudies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS). Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM). However, there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations.

METHODSWe prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011. They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS). Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2a (8-isoPGF2α). Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment. Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE), largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE). The correlations between glucose parameters and the index of oxidative stress were analyzed.

RESULTSUrine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs. (675.23±354.59) ng, P = 0.019). There was a correlation between urine 8-isoPGF2a level and MAGE (r = 0.321, P = 0.039), a significant correlation between low-density lipoprotein and urine 8-isoPGF2a level (r = 0.419, P = 0.03). There was no significant correlation between urine 8-isoPGF2α level and blood pressure, glycosylated hemoglobin (HbA1c), fasting C-peptide or other lipid indices.

CONCLUSIONA correlation between urine 8-isoPGF2a levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM.

Adolescent ; Blood Glucose ; metabolism ; Child ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; urine ; Dinoprost ; urine ; Female ; Humans ; Insulin ; therapeutic use ; Lipoproteins, LDL ; metabolism ; Male ; Oxidative Stress ; drug effects

Objective To establish cell strain expressing the genes of HIV vpr and mutant HIV vpr-FS, and to explore cell apoptosis ability by HIV Vpr and Vpr-FS. Methods The recombinant plasmids were constructed by cloning HIV vpr and HIV vpr-FS genes into the eukaryotic expression vector pcDNA3.1respectively. To determine the primary structures of HIV vpr and HIV vpr-FS, plasmids were cleaved by restriction enzymes. After the plasmids were transfected into HeLa cells by liposome, the HeLa cells were selected with G418 selective medium, mRNA expression of HIV vpr or HIV vpr-FS of transfected cells was detected by RT-PCR, and Vpr and Vpr-FS protein expression were detected by Western blot assay respectively. The DNA content and the percentage of apoptosis in HeLa HIV vpr cell, HeLa HIV vpr-FS cell and HeLa pcDNA3.1 cell were monitored by flow cytometry and the DNA fragmentation was analyzed by agarose gel electrophoresis. Results BamH Ⅰ and Hind Ⅲ cleavaged products of pcDNA3.1-vpr and pcDNA3.1-vpr-Fincluded 342 bp length fragments suggesting that the length of DNA sequence containing HIV vpr (HIV vpr-FS) within pcDNA3.1 was the same as theoretical length. The HeLa cells transfected by pcDNA3.1-vpr or pcDNA3, l-vpr-FS and selected with G418 could express HIV vpr or HIV vpr-FS by RT-PCR, and express HIV Vpr or HIV Vpr-FS protein by Western blot. The results of flow cytometry and DNA fragmentation showed that there was significant different in the number of apoptotic cells between HeLa HIV vpr cell and HeLa HIV vpr-FS cell, but the difference between HeLa HIV vpr-FS cell and control group was not obvious. Conclusion Recombinant plasmids pcDNA3.1-vpr and pcDNA3. 1-vpr-FS were constructed successfully, and the cell strain expressing HIV Vpr and HIV Vpr-FS proteins was established. The HIV Vpr could induce host cell apoptosis, while the mutant of Vpr did not or weakened this ability. This study provides foundation for further study on HIV vpr gene.

OBJECTIVE: To evaluate the long-term efficacy and safety of nevirapine (NVP)-based regimens for HIV-infected Chinese patients in routine clinical practice. METHODS: From October 2002 to May 2004, 57 HIV-1-infected patients commenced highly active antiretroviral therapy (HAART), and were followed to December 2008. They originally received 2 nucleoside reverse transcriptase inhibitors (NRTIs) and nevirapine. HIV RNA levels, T lymphocyte subsets and safety were assessed. Blood routine test and main laboratory parameter changes were traced. If apparent side effects or virological failure appeared we would, if necessary, terminate the therapy or change the regimen. RESULTS: Of the 57 subjects, 34 were followed-up for more than 4 years. After 5-6 years, 63.3% of the subjects (19/30) had HIV RNA levels<50 copies/microL, and the median increase in CD4(+) cell count from the baseline was 329 cells/microL. The mean decrease in CD8(+) cell count was 128 cells/microL. At the same time, the CD4(+) CD45RA+CD62L cell count and CD4(+)CD45RO(+) cell gradually increased, and the counts of CD8(+)CD38(+) cell declined gradually. These changes are apparent 2 years after HAART. The increase rate slowed down after 2 years. But they did not recover completely as well as healthy people at year 6. About 56% (32/57) of HIV-infected patients developed various drug-related side effects. The most common was gastrointestinal side effect, followed nervous disorder, baldness, and rashes, mostly happened in 6 months. Gamma-GT increased occurred in 29.8% of patients (17/57), and serum cholesterol and triglyceride elevated in 26.3% of the patients (15/57). Six patients developed lipodystrophy, mainly in female patients, and 25 patients showed abnormal blood picture and liver function, renal function changes and amylase elevation. Grade 3-4 adverse events occurred in 3 cases (2 peripheral neuropathy, and 1 suspected lactic acidosis). One subject experienced grade 3 rashes. CONCLUSION Antiretroviral therapy with NVP-based regimens is safe and effective by suppressing HIV viremia and producing continued CD4 cell increases in subjects with HIV or AIDS for 6 years.
Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; Antiretroviral Therapy, Highly Active ; adverse effects ; methods ; CD4 Lymphocyte Count ; China ; Didanosine ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; HIV Infections ; drug therapy ; virology ; HIV-1 ; drug effects ; isolation & purification ; Humans ; Male ; Middle Aged ; Nevirapine ; administration & dosage ; adverse effects ; Reverse Transcriptase Inhibitors ; administration & dosage ; adverse effects ; Stavudine ; administration & dosage ; adverse effects ; Treatment Outcome ; Viral Load ; Young Adult

Objective To compare the anterior-posterior decade glycemic control with improvement of diabetes management and evaluate the influence of socioeconomic factors on glycemic control.Methods This cross-sectional clinical-based survey enrolled 158 with type 1 diabetes mellitus (T1DM) children from Sep.2011 to May 2012 (group A) in Beijing Children's Hospital of more than 1 year management and compared with 123 children with T1DM who were recruited in Asia and the West Pacific Region T1DM Study from Sep.2001 to May 2002 (Group B) in Beijing Children's Hospital.Normally distributed data were reported,linear correlation and regression analysis were performed for glycemic control.Results There was no complication in the both groups.The average of hemoglobin A1C(HbA1C) in group A was (8.50 ± 1.53) ％,better than that of group B [(9.90 ± 1.85) ％,P =0.000].The ratio of optimal and suboptimal HbA1C in group A and group B were 15.0 ％ vs 10.6％,while the ratio of suboptimal HbA1C in group A and group B were 52.5 ％ vs 25.2％,respectively,there were significantly statistical differences (all P =0.000).The ratio of insulin injection twice daily in group A and group B were 43.0％ vs 92.6％,respectively and the ratio of multiple daily injection and continuous subcutaneous insulin injection were increasing significantly 10 years after.The frequency of self-monitoring blood glucose(SMBG) between 60-120 times per month and over 120 times per month in group A was 45.5％ and 37.8％,while 0.8％,0 in group B,respectively,there was significant statistical difference (P =0.000).HbA 1C was positively correlated with age,duration,insulin dosage per day while inversely correlated with frequency of SMBG in liner correlation and regression analysis.It was showed that duration was the most important factor for HbA1C.Conclusions There were younger with T1DM in Beijing Children's Hospital.The frequency of SMBG and the ratio of multiple daily injection and continuous subcutaneous insulin injection were increasing significantly after 10 years.Duration was the most important factor for glycemic control.There was no complication in children with T1DM.Glycemic control would be better due to improvement of SMBG and increase of the frequency of insulin injection.

OBJECTIVETo observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes.

METHODSC57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined.

RESULTSCompared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue.

CONCLUSIONNicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.

To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g•kg⁻¹ and 1.08 g•kg⁻¹). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g•kg⁻¹ water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats.

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.

PURPOSETo investigate the effects of estrogen G protein-coupled receptor 30 (GPR30) agonist G1 on hippocampal neuronal apoptosis and microglial polarization in rat traumatic brain injury (TBI).

METHODSMale SD rats were randomly divided into sham group, TBI + vehicle group, TBI + G1 group. Experimental moderate TBI was induced using Feeney's weigh-drop method. G1 (100μg/kg) or vehicle was intravenously injected from femoral vein at 30 min post-injury. Rats were sacrificed at 24 h after injury for detection of neuronal apoptosis and microglia polarization. Neuronal apoptosis was assayed by immunofluorescent staining of active caspase-3. M1 type microglia markers (iNOS and IL-1β) and M2 type markers (Arg1 and IL-4) were examined by immunoblotting or ELISA. Total protein level of Akt and phosphorylated Akt were assayed by immunoblotting.

RESULTSG1 significantly reduced active caspase-3 positive neurons in hippocampus. Meanwhile G1 increased the ratio of Arg1/iNOS. IL-1β production was decreased but IL-4 was increased after G1 treatment. G1 treatment also increased the active form of Akt.

CONCLUSIONSGPR30 agonist G1 inhibited neuronal apoptosis and favored microglia polarization to M2 type.

Animals ; Apoptosis ; drug effects ; Brain Injuries, Traumatic ; drug therapy ; pathology ; Cell Polarity ; Hippocampus ; drug effects ; Interleukin-1beta ; biosynthesis ; Male ; Microglia ; drug effects ; Neurons ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; agonists

China/epidemiology* ; Cognition ; Cross-Sectional Studies

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications