Aged ; Antineoplastic Agents ; therapeutic use ; B7-2 Antigen ; analysis ; Diagnosis, Differential ; Follow-Up Studies ; Histiocytic Disorders, Malignant ; drug therapy ; metabolism ; pathology ; Humans ; Male ; Sarcoma ; chemistry ; drug therapy ; pathology ; Skin Neoplasms ; chemistry ; drug therapy ; pathology

Adult ; Antigens, CD20 ; metabolism ; Antiviral Agents ; therapeutic use ; Bone Marrow Transplantation ; adverse effects ; CD3 Complex ; metabolism ; Epstein-Barr Virus Infections ; drug therapy ; etiology ; Follow-Up Studies ; Foscarnet ; therapeutic use ; Humans ; Ki-67 Antigen ; metabolism ; Lymphoproliferative Disorders ; drug therapy ; etiology ; immunology ; virology ; Male

Objective To investigate the in vitro inhibitory effects of regulatory T cells ( Treg ) from unpregnant mice and pregnancy-induced regulatory T cells ( piTreg) on the proliferation of na?ve T cells and their differences .Methods The numbers of piTreg cells from allogeneic pregnant mice ( C57/B6 fe-male×BALB/c male) on day 12.5 (E12.5d) of gestation and Treg cells from unpregnant C57/B6 mice were detected respectively by flow cytometry .The percentages of piTreg cells and Treg cells in CD 4+T cells of age-matched female mice and their intracellular expression of Foxp 3 were analyzed .The in vitro inhibitory effects of piTreg cells and Treg cells on the CFSE-labeled na?ve T cells ( effector cells ) were compared in a one-way mixed lymphocyte culture system using mitomycin C-inactivated CD4-T cells as stimulator cells . Results The level of piTreg cells in splenic mononuclear cells was significantly higher than that of Treg cells (P<0.001) from normal mice.Foxp3 was highly expressed in both piTreg cells and Treg cells , howev-er slightly increased in piTreg cells .Moreover , piTreg cells had a significant stronger in vitro inhibitory effect on na?ve T cells proliferation than that of Tregs cells (P<0.006), which was in a cell-dependent manner. Conclusion The present study suggests that the piTreg cells have a stronger inhibitory effect on na ?ve T cell proliferation as compared with Terg cells from unpregnant mice , The differential activity of CD 4+CD25+Treg might be mediated by the paternal antigens during pregnancy .

Background Optic neuropathy is one of the diabetic eye complications.Rosiglitazone,a peroxisome proliferator activated receptor γ(PPARγ) agonist,plays a very important role in arresting the pathogenesis and development of diabetes.However,the role of PPARγ in diabetic optic neuropathy is unclear.Objective This study was to investigate the protective effect of rosiglitazone against diabetic optic neuropathy and its mechanism.Methods Male Sprague-Dawley rats were randomly divided into the control group,diabetic group and rosiglitazone group,with 10 rats for each group.Diabetic models were induced by injecting 50 mg/kg of streptozotocin via the caudal vein,and rosiglitazone(5 ng/[kg· d])was used in the rats of the rosiglitazone group by intragastric administration every day for four weeks.At the end of the experiment,the fasting blood sugar(FBS) was tested in all the animals.The level of vascular endothelial growth factor(VEGF) in the blood plasma was detected by ELISA.Optical neural tissues were obtained from the rats of each group,and Lauck fast Blue myelin stain was used to examine the morphology of the optical myelin.The expression of neural cell adhesion molecule (NCAM) mRNA and protein in the optic nerve was detected by real time PCR and Western blot,respectively.Results The levels of FBS,blood plasma VEGF,NCAM mRNA and protein in the optic nerve were significantly different among the control group,diabetic model group and the rosiglitazone group after the administration of 5 nmg/(kg · d) rosiglitazone for 4 weeks (F =6.12,P＜0.01 ; F =5.14,P＜0.05 ; F =4.75,P＜0.05 ; F =4.87,P＜0.05).Compared with the control group,the level of FBS significantly increased in the diabetic model group(t =2.26,P＜O.05),and that in the rosiglitazone group significantly declined in comparison with the diabetic model group(t=2.08,P＜0.05).The optic nerve exhibited a normal morphology in the control group as revealed by the Lauck fast Blue myelin staining;however,severe demyelination of the optic nerve and proliferation of glial cells were found in the diabetic model group,and mild demyelination of the optic nerve and proliferation of glial cells were seen in the rosiglitazone group.Blood plasma VEGF was(28.76±4.21)ng/L in the control group and(134.28±11.36)ng/L in the diabetic model group,showing a significant difference between them (t=2.36,P ＜ 0.05).Compared with the model group,the blood plasma VEGF was significantly lower in the rosiglitazone group ([42.67 ± 5.83] ng/L) than that in the diabetic model group (t =2.17,P＜ 0.05).Expression of NCAM mRNA and protein in the optic nerve significantly decreased in the diabetic model group compared with the control group(t =2.21,t =2.58,both at P＜0.05);while those in the rosiglitazone group were significantly elevated in comparison with the diabetic model group(t =2.19,t =2.67,both at P＜O.05).Conclusions Rosiglitazone can protect optic nerve from damage in diabetic rats mainly by downregulating blood plasma VEGF level and upregulating NCAM expression.

Objective To investigate the clinical value of virtual touch tissues quantification in the evaluation of kidney stiffness in patients of diabetic nephropathy .Methods A total of 90 cases of diabetic nephropathy were divided into 3 groups:infinitesimal albuminuria ,microalbuminuria and massive proteinuria groups.And other 30 health subjects were taken as control group.The shears wave velocity ( Vs) which reflected the tissue elasticity was measured.The Vs values were compared among different groups.Results In all groups,the highest Vs was present in renal cortex .And compared with the renal cortex ,the Vs of the renal medulla and renal sinus have statistically significant differences [ the normal control group:( 3.65 ± 0.26)m/s,(2.72 ±0.35) m/s,(1.83 ±0.54) m/s,t =9.30,18.20,both P <0.05;Infinitesimal albuminuria group:(2.98 ±0.28)m/s,(2.47 ±0.33)m/s,(1.65 ±0.31)m/s,t=5.97,15.57,both P<0.05;microalbuminuria group:(2.55 ±0.22) m/s,(2.22 ±0.28) m/s,(1.54 ±0.21) m/s,t =3.86, 11.83,both P<0.05;massive proteinuria group:(1.99 ±0.28)m/s,(1.49 ±0.30)m/s,(1.01 ±0.39)m/s, t=5.85,11.48,both P<0.05].The renal cortex Vs of Infinitesimal albumonuria group ,microalbuminuria group and massive proteinuria group show a gradually decreasing trend .And the renal cortex Vs of microalbuminuria group and massive proteinuria group have statistically significant differences compared with the normal control group(t=11.79,17.79,both P<0.05).Conclusions Virtual touch tissues quantification technique can reflect the renal tissue elasticity .It will contribute to the assessment of renal function in patients with early diabetic nephropathy .

OBJECTIVE To observe the effect of dihydromyricetin (DMY) on cell injury induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells and explore the possible mechanism. METHODS After being pretreated with DMY 5, 10, 20, 40 and 80 μmol · L-1 for 0.5 h, PC12 cells were incubated with DMEM culture medium including autophagy inhibitor 3-methyladenine (3-MA) 10 mmol · L-1 and MPP+500μmol·L-1 for 48 h. MTT Assay was used to test the viability of PC12 cells. The level of lactate dehy-dregenase (LDH) was measured colorimetrically. The ultrastructure of PC12 cells was observed under transmission electron microscope. Expressions of autophagy related protein, Beclin-1, microtubule-associated protein light chain 3 (LC3) and p62 were measured by Western blotting. RESULTS Compared with cell control group, the cell survival rate was significantly decreased, the level of LDH was signifi-cantly increased, the number of autophagosomes was obviously decreased, the percentage of autophagic vacuoles in the total cytoplasm area was significantly decreased (P<0.05), expression of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ to LC3-Ⅰ were significantly down-regulated (P<0.05) and the expres-sion of p62 was significantly up-regulated in MPP+group (P<0.05). Compared with MPP+group, the cell survival rate was significantly increased, while the level of LDH was significantly decreased in MPP++DMY 10-80 μmol · L-1 group (P<0.05). Compared with MPP+ group, the number of autophagosomes obviously increased, the percentage of autophagic vacuoles in the total cytoplasm area was significantly increased, the expression of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ to LC3-Ⅰwere significantly up-regulated and the expression of p62 was significantly down-regulated in MPP++DMY 20 μmol · L-1 group (P<0.05). Compared with MPP++DMY 20μmol · L-1 group, the cell survival rate was significantly decreased, but the level of LDH was significantly increased in MPP ++DMY+3-MA group (P<0.05). CONCLUSION DMY may inhibit the cell injury induced by MPP+in PC12 cells, and the mechanism may be related to the up-regulation of autophagy activity induced by DMY.

The purpose of the present study was to investigate the effect of 17beta-estradiol (17beta-E(2)) on the structure and relaxation and contraction activity of thoracic aortas in ovariectomized rats with insulin resistance induced by fructose. Ovariectomized mature female Sprague-Dawley rats were fed with high fructose diet for 8 weeks to induce insulin resistance. Physiological dose of 17beta-E(2) (30 mug/kg) was injected subcutaneously every day for 8 weeks. Systolic blood pressure (SBP) was measured by use of tail-cuff. Serum nitric oxide (NO), estradiol (E(2)), fasting blood sugar (FBS) and fasting serum insulin (FSI) were measured respectively in each group. The insulin sensitive index (ISI) was calculated. The thoracic aortas were fixed in formalin, sliced and HE dyed. The structure of thoracic aortas, lumen breadth, media thickness, media thickness/lumen breadth ratio and media cross-section area were measured. The contraction response of thoracic aorta rings induced by L-phenylephrine (PE) and the relaxation response of thoracic aorta rings induced by ACh and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) was used. The results obtained are as follows: (1) 17beta-E(2) protected against the effect of high fructose diet, which caused an increase in SBP, hyperinsulinemia and a decrease in ISI in ovariectomized rats. (2) The structure of thoracic aortas had no significant difference among the groups. (3) Compared with the ovariectomized group (OVX) or fructose fed group (F), serum nitric oxide was significantly reduced, the contraction response of thoracic aorta rings to PE was enhanced and the relaxation response to ACh was depressed significantly in ovariectomized+fructose fed group (OVX+F). The effect of high fructose was reversed by 17beta-E(2). After pretreatment with L-NAME, the effect of 17beta-E(2), which enhanced the relaxation response of thoracic aorta rings to ACh in ovariectomized+fructose+17beta-E(2) group (OVX+F+E(2)), was partly blocked. (4) The relaxation response of thoracic aorta rings to SNP had no significant difference among the groups. (5) The contraction response of thoracic aorta rings without endothelium to PE had no significant difference among the groups. These findings suggest that 17beta-E(2) may provide protection against the effect of high fructose diet, which causes hypertension, dysfunction of endothelial cells and insulin resistance. The mechanism of this effect of 17beta-E(2) could be partly associated with the increase of NO by NOS pathway, or associated with the decrease in the level of systolic blood pressure and serum insulin, and the improvement of insulin resistance.
Animals ; Aorta ; physiology ; Estradiol ; pharmacology ; Female ; Fructose ; Insulin Resistance ; physiology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasomotor System ; drug effects

Rosiglitazone (ROSI), thiazolidione peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator, reduces insulin resistance in patients with type 2 diabetes (T2DM). It also improves vascular reactivity in T2DM patients and some animal models by unclear mechanisms. In order to investigate the effect of ROSI on aortic systolic and diastolic function of insulin resistant-hypertensive rats (IRHR) and the underlying mechanism, male Sprague-Dawley (SD) rats were fed with high fructose (HF) for 8 weeks to induce IRHR model. To verify IRHR model, systolic blood pressure (SBP), fasting blood sugar (FBS), fasting serum insulin (FSI) were measured respectively in each group, and insulin sensitive index (ISI) was also calculated. Subsequently, the vascular function test was performed. The thoracic aortic ring of SD rats was mounted on a bath system. The effect of rosiglitazone on the contraction elicited by L-phenylephrine (PE) and potassium chloride (KCl) and the relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was used and serum nitric oxide (NO) was measured. The results obtained were as follows: (1) Rosiglitazone reduced the level of SBP, serum insulin and improved insulin resistance in IRHRs. (2) The contractive responses of thoracic aortic rings to PE and KCl were enhanced and the relaxation response to ACh was depressed significantly in the HF group, and the effect was reversed by ROSI. (3) After pretreatment with L-NAME, the relaxation response to ACh was further impaired in the HF group, this effect was partly reversed by ROSI. (4) Sodium nitroprusside (SNP)-induced vasodilator responses did not differ significantly among the groups. (5) Aortic systolic and diastolic function of the control group was not affected markedly by ROSI. (6) Compared with the control group, serum nitric oxide was significantly reduced in the HF group, but after rosiglitazone treatment it was remarkably increased. These findings suggest that ROSI can improve aortic diastolic function of insulin resistant-hypertensive rats, the mechanism of this effect might be associated with an increase in nitric oxide mediated partly by NOS pathway, a decrease in the level of blood pressure, serum insulin and the improvement of insulin resistance.
Animals ; Aorta ; drug effects ; physiopathology ; Hypertension ; drug therapy ; physiopathology ; Insulin Resistance ; Male ; Nitric Oxide ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones ; pharmacology ; therapeutic use ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; therapeutic use

OBJECTIVETo understand the reproductive health status of female workers in pharmaceutical industry of Gansu Province, to explore influencing factors, and to propose some reference basis of intervening measures.

METHODSThe cluster sampling method was used to study 1801 female workers from 16 pharmaceutical industries in 6 cities (Pingliang, Qingyang, Lanzhou, Dingxi, Zhangye and Jiuquan cities) of Gansu Province. The investigation was performed by interviewing and adopting questionnaires.

RESULTSThere were the problems of labor and organization, which included the overtime work, continuous work, standing for long periods, rapid monotonous action assignments, the loading work and a variety of harmful factors in the working environment of the pharmaceutical industry in Gansu Province. There were many problems in the reproductive health status of female workers. The morbidities of abnormal menstruation and breast diseases in female workers were 43.25% and 20.43%. The order of high morbidities was hyperplasia of mammary glands (91.30%), breast adenofibroma (5.43%) and mastitis (2.99%). The order of morbidities for three reproductive system disease was adnexitis (21.57%), cervical erosion (20.06%) and vaginitis (11.09%). The rates of abnormal menstrual cycle, abnormal menstrual amount and cervical erosion increased with the length of service (P < 0.01). The taking breaks, long standing, loading work, exposure to harmful factors were related to abnormal menstruation (P < 0.05). The rapid repeat monotonous action was an important influencing factor for female reproductive system disease (OR = 1.255, 95%CI = 1.031 ∼ 1.528).

CONCLUSIONThere are relatively serious occupational hazards in the pharmaceutical industry of Gansu Province. The reproductive health status of female workers is not improved. Social public should pay attention to the protection for female workers.

Adolescent ; Adult ; China ; Drug Industry ; Female ; Health Status ; Humans ; Middle Aged ; Occupational Exposure ; Reproductive Health ; Surveys and Questionnaires ; Workplace ; Young Adult

OBJECTIVETo explore toxicokinetics of tetramethylene disulphotetramine (TETS) in rabbit and the effects on toxicokinetics of TETS after activated charcoal by gavage.

METHODSEight rabbits were exposed through gavage and vein respectively, the blood samples were collected from the center artery in ear of rabbit at an arranged time. Four rabbits were exposed after being intubated into urethra and common bile duct. The samples of bile and urine were collected at arranged times. After being exposed by gavage, activated charcoal (1 g/kg) was administrated in the activated charcoal group and the distilled water (1 g/kg) administrated to the controls. The samples of blood were collected from the center artery in ear of rabbit at arranged times. The contents of TETS in samples were determined by GC/NPD method. Analysed by the 3p87 soft, toxicokinetics parameters of TETS were acquired.

RESULTSTETS was eliminated very slowly in rabbit. The plasma half time in elimination phase (Tke1/2) of TETS was 56.9 hours in vein exposure group and 262.5 hours in oral exposure group respectively. The plasma clearance (CL) of it was only 15.4 ml.kg(-1).h(-1) in oral exposure group and 24.1 ml.kg(-1).h(-1) in vein exposure group. TETS was eliminated from urine in rabbit. The eliminated amount of it from urine was more 5 times than from bile. All parameters of toxicokinetics of TETS were significantly different between the activated charcoal group and the control. Compared to the control, Tke1/2 of TETS in the activated charcoal group was equal to 55%, CL was increased over 3-fold, area under the curve was equal to 30%.

CONCLUSIONTETS was a poison eliminated very slowly in body. The eliminated amount of it from urine was more than from bile. The excretion of TETS could be quickened after activated charcoal by gavage.

Animals ; Antidotes ; administration & dosage ; Bile ; metabolism ; Bridged-Ring Compounds ; blood ; pharmacokinetics ; urine ; Charcoal ; administration & dosage ; Female ; Male ; Metabolic Clearance Rate ; drug effects ; Rabbits