Objective To study the effect of renal p53 protein expression on kidney development in rats with intrauterine growth restriction ( IUGR) . Methods Pregnant rats were randomly assigned into normal group, IUGR group and L-Arg treated group. Normal group were fed with normal diet (21％protein). IUGR group and L-Arg treated group were fed with low-protein diet (10％ protein). During lactation, maternal rats in the three groups were all fed with normal diet. Maternal rats in L-Arg treated group were given additional special drinking water ( L-Arg:200 mg/kg) , while maternal rats in normal and IUGR group were given normal drinking water. Offspring weaned after 21 d and had free access to normal rodent diet and water. When the pups grew up to 2 m, the number of glomeruli was counted using acid digestion method, the proliferation and apoptosis of glomerular and tubular cells were studied using TUNEL and Ki-67 immunohistochemistry, and the ultrastructure of epithelial cells was determined by electron microscopy. At 7 d, 21 d, 2 m and 3 m, p53 protein expression in renal tissue was measured by Western blot, respectively. Results At 2 m, the number of glomerulus ( right kidney) in IUGR group was significantly lower than normal group [(23 647±541) vs. (27 689±492), P＜0. 01]; the index of renal cell apoptosis in IUGR group was higher than normal group [(21. 9 ± 2. 0) vs. (16. 7 ± 2. 5), P＜0. 05];however, IUGR group and normal group had no statistically significant difference (P＞0. 05). The proliferation of mesangial cells was found in IUGR and L-Arg treated group, but not in normal group. And the extent of proliferation in L-Arg treated group was lesser than IUGR group. A reduction of foot process and partial fusion of foot process could be observed in IUGR group and L-Arg treated group while the foot process morphology in normal group was normal. At 2 m and 3 m, p53 protein level in IUGR group and L-Arg treated group were higher than normal group [ 2 m: ( 0. 28 ± 0. 03 ) and ( 0. 21 ± 0. 01 ) vs. (0. 10±0. 02);3 m:(0. 39±0. 04) and (0. 26±0. 02) vs. (0. 17±0. 03);P＜0. 01], while IUGR group higher than L-Arg treated group ( P＜0. 05 ) . Conclusions The kidney of IUGR rats showed reduced glomerular number, increased renal cell apoptosis, enhanced p53 protein expression, increased proliferation of glomerular mesangial cells, decreased foot process, and partial fusion of foot process. And L-Arg could to some extent improve the organizational structure of the kidney in IUGR rats.

Objective To investigate the effect of p53-gene expression on renal function in rat with low birth weight ( LBW) .Methods Fifteen pregnant rats were randomly assigned into normal group, LBW group, and L-arginine ( L-Arg)-treated group.For normal group, pregnant rats were fed with 21% protein diet during pregnancy.For LBW and L-Arg treated groups, rats were fed with 10%protein diet.After de-livery, all rats were fed with 21%protein diet.For L-Arg-treated group, rats were given a supplementation with L-Arg (200 mg/kg) drinking water during 21 d lactation, other rats were given running water.At the age of 2m, the ultrastructural change in mesangial cell and podocyte was observed with electron microscope. At the age of 7 d, 21 d, 2 m, and 3 m old, the p53 mRNA expression in renal tissues was observed with re-verse transcription polymerase chain reaction ( RT-PCR) , blood and urine were collected to detect biochem-ical indicators of renal function and 24 h-urine protein.Results ⑴At the age of 3 m,the blood urea nitro-gen ( BUN) and urine cretinine ( UCr) in normal group were significantly lower than those in LBW group ( P <0.01).Compared to normal group, the Ucr of LBW group was significantly lower at the age of 2 m ( P<0.05).At the age of 3 m,the Ucr of L-Arg treated group and LBW group was significantly lower ( P <0.05), the level of 24 h-Urine protein was notably increased in LBW group and L-Arg treated group than that in normal group ( P <0.01, P <0.05) .⑵At the age of 3 m,the expression of p53 mRNA in LBW group was higher obviously than that in normal group.There is a significantly negative correlation between the expression of p53 mRNA and the level of Ucr in LBW group ( r =-0.91, P <0.05).⑶ There were mesangial cell proliferation with matrix increase, filtration membrane podocyte reduction, and partially dis-solved in LBW group, the mesangial cell proliferation of L-Arg treated group was decreased compared to that in LBW group.Conclusions The higher expression of p53 gene in LBW group might be one of reasons for the decreased renal function in LBW rats.

Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy (LVH) in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism in Chinese. Methods We recorded 12-lead ECG (CardioSoft, v4.2) in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Comell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Comell product ECG criteria was used, the prevalence of LVH (20.7% and 4.8%, respectively) significantly (P<0.0001) increased with male gender (odds ratio [OR] 2.33 and 7.15) and systolic blood pressure (per 10 mm Hg increase, OR 1.46 and 1.33). If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake (OR 1.44, P=0.03) and body mass index (OR 0.83, P=0.0005). The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy (P=0.01). In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with Ⅱ subjects had significantly higher Sokolow-Lyon voltage amplitudes (29.8±0.6 vs. 28.0±20.5 mV, P=0.02) and higher risk of LVH (OR 1.74, 95% CI: 1. 12-2.69, P=0.01). Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy.

Objective To evaluate the running status of the water-improving projects in Gansu Province in order to further improve the supervising mechanism and raise the efficiency of defluoridation in drinking water.Methods The water-improving projects,either being normal,or intermittent,or discarded and the cause of abnormal running in 33 counties in Gansu Province were surveyed with unified standard method.Fluoride content in water was determined by F-ion selective electrode.Results 993 water improving projects covering 3389 fluorosis villages were surveyed,682 projects worked well[68.68%(682/993)]and had supplied water with normal fluoride contents to 2174 villages[64.15%(2174/3389)]and benefited 116.56 hundred thousand populations.And the rest 311[31.32%(311/993)]projects worked abnormally or supplied unqualified fluoride water.The main causes were the exceeded lasting life,insufficiency of water resources,high fluoride content in water and unqualified administration.Conclusions Most of the water-improving projects in Gansu Province are basically running normally,but about 1/3 of the projects do not function well,so the management of the projects must be improved and consummated.

Objective To study the changes of plasma cystatin C level (PcyC),and evaluate the effects of the joint use of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline lesion of coronary artery.Methods One hundred and thirty consecutive patients with borderline coronary lesion assessed by quantitative coronary angiography were enrolled into borderline coronary lesion group (BCL),and another 136 subjects without coronary lesion were enrolled as controls (CTR).And in the meantime,the subjects in BCL group were randomized (closed envelope method) into routine treatment subgroup ( RTT,n =60),and combined treatment subgroup in which patients were treated with atorvastatin 20 mg plus probucol 1.0 g daily in addition to routine medication ( CBT,n =70) for 6 months.There were no statistical differences in basic clinical features between two subgroups.PcyC,high-sensitive C-reactive protein (hs-CRP),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol ( HDL-C ) and triglycerides (TG) were determined.Of them,104 patients in BCL group rechecked by coronary angiography.Comparison of biomarkers carried out between two groups by using a number of independent-sample t-test and analysis of variance.For enumeration data,chi-square test was used to compare mean values of biomarkers between groups. P ＜ 0.05 was considered statistically significant.Results PcyC levels were significantly higher in BCL group than those in CTR group ( P ＜ 0.05 ).Compared with RTT subgroup,levels of PcyC,TC,LDL-C,TG and hs-CRP were more significantly decreased in CBT subgroup (P ＜ 0.05,P ＜ 0.01 ).Moreover,there was a trend of slight decrease in the mean percent of stenosis (MPS) of coronary artery with borderline lesion in RTT subgroup treated for 6 months,whereas more marked decrease in the MPS of coronary artery with borderline coronary lesion in CBT subgroup treated for 6 months ( P ＞ 0.05 ; P ＜ 0.05 ).Conclusions Cystatin C plays an important role in the pathogenesis of coronary artery,and PcyC is associated with severity of coronary lesion,the combination of atorvastatin and probucol decreases the PcyC level,and it may be the treatment of choice for borderline lesion of coronary artery.

This study examined the prevalence of primary open-angle glaucoma (POAG) among residents aged &ge;50 years living in Yongchuan district of Chongqing. Stratified cluster sampling was employed in random selection to estimate the prevalence of glaucoma from April to June, 2005. Twenty-nine villages or neighborhood communities were randomly selected in urban area (Zhongshan Road), suburban area (Shanjiao Town) and exurban area (Zhutuo Town) of this district. All the respondents underwent detailed ophthalmic examinations. The examinations included questionnaire investigation, visual acuity test, naked-eye examination, measurement of peripheral anterior chamber depth (Van Herrick's technique), detection of intraocluar pressure (IOP) with a Perkins hand-held applanation tonometer (HA-2) and examination of the optic disc by using a 78 diopters (D) lens (including the cup-disc ratio, cup/disc ratio asymmetries, horizontal and vertical diameter, notching and optic disc hemorrhages). A total of 5938 residents were actually examined, and the response rate was 85.19%. The crude prevalence of POAG was 0.86% (n=51/5938, 95% CI 0.64%-1.11%). There were 24 males and 27 females in the glaucoma group. The glaucoma prevalence was not significant different in case number between the male and female subjects (P=0.4900). Furthermore, no association between age or schooling and POAG was noted (P=0.8030, 0.0734). Out of 51 subjects with POAG, unilateral glaucoma-related blindness occurred in 38 subjects (74.5%) and bilateral glaucoma-related blindness was found in 7 subjects (13.7%). This study exhibited that the prevalence of POAG was 0.86% among residents aged &ge;50 years living in Yongchuan District of Chongqing. The vision loss caused by POAG in this population was obviously higher than that previously reported in other studies. Glaucoma management, detection of affected persons and handling of the burden of glaucoma should be the priorities of the agenda of local health authorities of Western China.
Aged ; Blindness ; diagnosis ; epidemiology ; China ; epidemiology ; Female ; Glaucoma, Open-Angle ; diagnosis ; epidemiology ; physiopathology ; Gonioscopy ; methods ; Health Surveys ; methods ; statistics & numerical data ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Prevalence ; Surveys and Questionnaires ; Vision Disorders ; diagnosis ; epidemiology

OBJECTIVETo evaluate effects of celecoxib (a selective cox-2 inhibitor)combined with fluvastatin (a HMG-CoA reductase inhibitor) on tumor growth and cell apoptosis in hepatocellular carcinoma xenograft in nude mice.

METHODSHepatocellular carcinoma BEL-7402 cells were inoculated subcutaneously into the left armpit of nude mice, the mice (n = 32) were then randomly divided into 4 groups: the control group, the celecoxib group,the fluvastatin group and the combination group. At the end of the study, Tumor Tissues were collected for analysis. Cell apoptosis was determined by flow cytometry analysis and TUNEL assay. Akt, p-Akt and survivin protein levels were measured by Western blot. Statistical comparisons were made using factorial analysis of variance (ANOVA) and multiple comparisons between each two groups were calculated using SNK-q test.

RESULTSThe combination of Celecoxib and fluvastatin resulted in a greater inhibition of tumor growth than either agent alone, the tumor inhibitory rate was 34.0% in the Celecoxib group, 25.0% in the fluvastatin group and 72.2% in the combination group. The percentages of TUNEL--positive cancer cells in the celecoxib and fluvastatin alone treatment groups were 8.5%+/-1.4% and 9.4%+/-1.7% respectively as compared to the control group which was 3.5%+/-0.8%. Combination therapy showed a significantly greater increase in tumor cell apoptosis in comparison with the control and single-therapy groups (apoptotic index: 19.4%+/-3.0%; P value is less than 0.01 versus celecoxib or fluvastatin groups). The results of flow cytometry analysis also showed the same tendency. a small number of apoptotic cells were detected in the control tumours (4.1%+/-1.6%), whereas a large number of apoptotic cells were detected in tumours treated with celecoxib (9.1%+/-2.1%) or fluvastatin (10.1%+/-2.3%) alone; and the combination therapy resulted in even more apoptotic cells (23.6%+/-5.8%; P value is less than 0.01 versus celecoxib or fluvastatin groups). Western blot analysis demonstrated that the combination of celecoxib and fluvastatin significantly down-regulated p-Akt (0.23+/-0.08 versus 1.12+/-0.07 and surviving (0.50+/-0.07 versus 1.47+/-0.19) in BEL-7402 tumours compared with the control (P value is less than 0.01 for all).

CONCLUSIONThe present study provided evidence that treatment with celecoxib in combination with fluvastatin resulted in the inhibition of HCC tumour growth in an in vivo mouse model.

Animals ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; pathology ; Celecoxib ; Cell Line, Tumor ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacology ; Fatty Acids, Monounsaturated ; administration & dosage ; pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; pharmacology ; Indoles ; administration & dosage ; pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Pyrazoles ; administration & dosage ; pharmacology ; Sulfonamides ; administration & dosage ; pharmacology ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism.

METHODSTwo-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10-min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions.

RESULTSHistological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P < 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates (P < 0.01 vs 10-min ischemia group).

CONCLUSIONIschemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.

Animals ; Brain Ischemia ; pathology ; Cell Count ; methods ; Cell Death ; Disease Models, Animal ; Gene Expression Regulation ; physiology ; HSP70 Heat-Shock Proteins ; metabolism ; Hippocampus ; blood supply ; metabolism ; pathology ; Ischemic Preconditioning ; Male ; Neurons ; metabolism ; Proteins ; metabolism ; Rats ; Rats, Wistar ; Time Factors

Objective To investigate the distribution of water fluoride and the present status of water- improving delluoridation projects in the endemic fluorosis areas in Gansu Province. Methods According to "The National Technical Scheme for Endemic Disease Control in 2004" for the water improving projects, water fluoride content was determined from fluorosis villages in 34 counties of 11 cities in Gansu Province. The fluoride content in drinking water was assessed by F-ion selective electrode. Results Water fluoride content was determined in 1576 fluorosis villages of 34 counties. Water fluoride content of 7829 water samples was determined, and the fluoride content of 1891 samples was over standard. Water fluoride content was ≤ 1.00 mg/L(accounting for 75.19%) in 1185 villages and 1.00 mg/L(accounting for 24.81%) in 391 villages; the highest water fluoride content was 6.78 mg/L Nine hundred and ninety three water-improving and defluoridation projects were determined. Water fluoride content of 867 water-improving and defluoridation projects was determined; 768 projects had water fluoride content ≤1.00 mg/L(accounting for 87.67%) and water fluoride content of 108 projects was 1.00 mg/L(accounting for 12.33%),with the highest water fluoride content being 5.27 mg/L. Water-improving and delluoridation projects mostly relied on drilling a well to obtain under-grand water. Abandoned projects accounted for 30%. Conclusions In 34 counties of 11 cites(prefecture), nearly 30% of the villages had water fluoride content exceeding the standard. The situation of endemic fluorosis control is still serious in Gausu Province, countermeasures for endemic fluorosis must be carried out as soon as possible and surveillance of water-improving and defluoridation projects must be strengthened.

OBJECTIVETo explore the dynamic postburn changes in rat hepatic function and the effects of hyperoxic Ringer's solution resuscitation on the function.

METHODSOne hundred and ninety Wistar rats of both sexes with body weight of 250 - 300 g were employed as the model and were divided into 6 groups as A, B, C, D, E and F groups as follows: normal control (A, n = 10), early resuscitation with Ringer's solution (B, n = 40), delayed resuscitation with Ringer's solution (C, n = 30), early resuscitation with hyperoxic Ringer's solution (D, n = 40), delayed hyperoxic Ringer's solution resuscitation (E, n = 30) and burn control (F, n = 40). Blood samples were drawn from the injured rats under anesthesia at 6, 12, 24 and 48 postburn hours (PBHs), and the serum contents of ALT, AST and MDA in these blood samples were determined. Hepatic tissue samples were also harvested at the same time and served histologically.

RESULTSThe plasma ALT level at 6 PBH in all groups was higher than that in A group (P < 0.05). There was significant difference of plasma ALT levels between hyperoxic Ringer's solution treatment group an other treatment groups (P < 0.05). And there was evident difference of plasma ALT levels between hyperoxic Ringer's solution treatment groups and other treatment groups (P < 0.05). The dynamic change in plasma AST was almost similar to that of ALT. The plasma MDA level was increased obviously after injury, especially in F group (highest level). Furthermore, the MDA level in C group was higher than that in B group. The plasma MDA levels in D and E groups were evidently lower than that in all other groups (P < 0.05). It was revealed by histological examination that there were different degrees of degeneration an necrosis of hepatocytes during early postburn stage, but less so in D group.

CONCLUSIONFluid resuscitation during early postburn stage with hyperoxic Ringer's solution could inhibit the production of oxygen free radicals and blunt lipid peroxidation, and it could also enhance the host tolerance to hypoxia and prevent hepatocytes from injury, thus hepatic function was protected.

Animals ; Burns ; metabolism ; therapy ; Fluid Therapy ; Hepatocytes ; drug effects ; pathology ; Isotonic Solutions ; therapeutic use ; Liver ; metabolism ; pathology ; Oxygen ; administration & dosage ; Rats ; Rats, Wistar ; Shock, Traumatic ; metabolism ; therapy