To compare the anxiolytic effects of reduced metabolite of progesterone and benzodiazepine.Methods　The effects of allopregnanolone and diazepam on spontaneous locomotor activity and on exploration in the elevated plus-maze were studied in C57 mice 20 min after vehicle or drug intraperitoneal administration.Results Allopregnanolone (0.1 mg.kg-1,ip) elicited marked anxiolytic effects in terms of significantly reducing the latency to enter the open arm from (31.30±8.39)s to (8.80±6.00)s,(P<0.001),and significantly increasing both the number of open arm entries from 1.20 ± 0.42 to 4.80 ±1.75,(P<0.001) and the proportion of total time spent on the open arm from 7.13％ to 32.50％,(P<0.001).Meanwhile,the diazepam (0.25 mg·kg-1) produced a lower anxiolytic effect comparing to that of the allopregnanolone.Analysis of spontaneous locomotor activity showed while 0.5 mg·kg-1 of diazepam decreased the locomotor activity (P<0.01),neither 0.1 mg·kg-1 of allopregnanolone nor 0.25 mg·kg-1 of diazepam affect the locomotor activity score.Conclusion Together,these results provide evidence for differential behavioral actions of the neurosteroids and benzodiazepines.Since the allopregnanolone produce a selective anxiolytic effect without affecting the spontaneous locomotor activity,the allopregnanolone may be a better alternative for diazepam in treating anxiety.

Aim To compare the anxiolytic effects of reduced metabolite of progesterone and benzodiazepine.Methods The effects of allopregnanolone and diazepam on spontaneous locomotor activity and on exploration in the elevated plus_maze were studied in C57 mice 20 min after vehicle or drug intraperitoneal administration. Results Allopregnanolone (0.1 mg?kg-1, ip) elicited marked anxiolytic effects in terms of significantly reducing the latency to enter the open arm from (31.30?8.39)s to (8.80?6.00)s, (P

Objective To investigate the relationship between alteration of gene in cyclic adenosine monophosphate(cAMP) signal transduction system in rats after myocardial damage and changes of cardiac function and ventricular remodeling. Methods Twenty eight male Wistar rats weighing 220 g to 250 g were randomly divided into three groups: acute myocardial damage group(AMD, n = 10), chronic myocardial damage group (CMD,n = 9 ) and sham-operation group (control, n = 9). Animal model of acute myocardial damage was established by ligation of rats left coronary artery in the AMD and the CMD groups. Rats in control group were treated similarly, except that the coronary suture was not tied. Hemodynamics and echocardiography were measured before rats were sacrificed 24 hours after operation in control and AMD groups but those in CMD groups were sacrificed 8 weeks later. Cadiocyte apoptosis were estimated by TUNEL method, cAMP levels in heart were tested by radioimmunity and the mRNA expressions for inducible cAMP early repressor (ICER), cAMP response element binding protein (CREB), phosphodiesterase 3A (PDE3A) and bcl-2 were assayed by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results The difference of left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic pressure(LVEDP), maximal rising and falling rate of ventricular pressure,left ventricular systolic pressure (LVSP), eject fraction (EF) and fraction shortening (FS) were statistically significant among the three groups(F = 285.9, 196.8, 83.2, 80.4, 54.9, 196.6, 95.2, all P ＜ 0.01). LVEDD[(7.03 ±0.28), (8.20 ± 0.27)mm] and LVEDP[(11.19 ± 2.89), (19.76 ± 3.34)mmHg] in AMD and CMD groups were significantly increased, compared with those in control group[ (5.05 ± 0.30)mm, (- 5.62 ± 3.01 )mmHg, all P ＜0.01 ]. While maximal rising rate[ (2964 ± 449), (2214 ± 434)mmHg/s] and falling rate[(- 2617 ± 441),(- 1891± 424)mmHg/s] of left ventricular pressure, LVSP[ (94.19 ± 4.03), (85.85 ± 6.39)mmHg], EF[ (41.6 ±5.9)%, (35.9 ± 4.1 )%] and FS[ (36.9 ± 4.6)%, (23.1 ± 4.9)%] of left ventricular in the two groups were lower than those in control[(4759 ± 406)mmHg/s, (- 4327 ± 388)mmHg/s, (116.29 ± 8.25)mmHg, (80.9 ± 5.6)%,(53.1 ± 4.3)%, all P ＜ 0.01 ]. These changes in CMD group were more significant than those in AMD groups(P ＜0.05 or P ＜ 0.01 ). The difference of apoptotic index, cAMP and expression of ICER, CREB, PDE3A mRNA and bcl-2 mRNA were statistically significant among the three groups(F= 172.5, 141.0, 540.8, 246.8, 165.1, 563.9,all P＜ 0.01 ). Apoptotic index[ (32.8 ± 4.2)‰, (18.4 ± 3.9)‰] and cAMP in heart[ (9.95 ± 0.30), (5.60 ± 0.25)nmol/kg] in AMD and CMD groups were increased compared to control group[ (3.9 ± 1.7)‰, (2.48 ± 0.29)nmol/kg,all P ＜ 0.01 ], and those in CMD group were lower than in AMD group(all P ＜ 0.01 ). Expression of ICER mRNA (1.434 ± 0.093, 0.942 ± 0.076) and CREB mRNA(5.70 ± 0.50, 2.64 ± 0.51) in AMD and CMD groups were higher, and expression of PDE3A mRNA(48.98 ± 8.14, 16.68 ± 8.46) were lower than those in control group (0.154 ± 0.063, 1.08 ± 0.35, 105.94 ± 12.61, all P ＜ 0.01 ). The three genes in CMD group were fewer than those in AMD group(all P ＜ 0.01 ). bcl-2 mRNA was up regulated in AMD group(4.55 ± 0.27) and was down regulated in CMD group(0.35 ± 0.15) compared to control(2.18 ± 0.30, all P＜ 0.01). Conclusions There is PDE3A-ICER positive-feedback loop leading to myocyte apoptosis and heart failure after myocardial damage. The downregulation of PDE3A mRNA observed in chronic myocardial damage may play a causative role in the progression of ventricular remodeling and heart failure, in part, by inducing ICER mRNA and promoting cardiac myocyte dysfunction.

Objective To investigate the prevalence of endemic fluorosis in Guide county of Qinghai province, in order to provide appropriate measures to monitor and control the disease. Methods Damo, Wenquan, Baoning villages(water source has been changed) and Taiping village(water source has not been changed) in Guide county were involved in the study in 2008. One tap water sample was collected in dry and rainy seasons, respectively. Water fluoride was tested in accordance with the "Standard Test Methods for Drinking Water" (GB/T 5750.5-2006); of all the children aged 8 to 12, dental fluorosis was diagnosed using Dean criteria; 6 copies of urine samples were collected in each age group, urinary fluoride was measured using fluoride ion-selective electrode (WS/T 89-1996). According to the "Clinical Diagnostic Criteria of Endemic Skeletal Fluorosis "(WS 192-2008), clinical skeletal fluorosis was determined in adults over the age of 16 by X-ray examination for 10 people in each selected village. Results The mean water fluoride was 0.58,0.38,2.28,0.37 mg/L in Damo, Wenquan, Taiping, and Baoning villages, respectively, and that of Taiping village exceeded the national standard(1.0 mg/L). One hundred and ninety-three children aged 8-12 were checked, the detection rate of dental fluorosis was 49.74% (96/193); urine samples of 116 children were tested, median urinary fluoride was 1.49 mg/L A total of 1503 adults over the age of 16 were examined, the clinical detection of skeletal fluorosis was 51.63%(776/1503); a total of 82 people were X-rayed, X-ray detection of skeletal fluorosis was 20.73%(17/82). The characteristic of X-rays were degeneration and ossification of interosseous membrane. Conclusions Prevalence of dental fluorosis of children and adult clinical skeletal fluorosis are higher. The endemic fluorosis is still comparatively serious. Prevention efforts need to be further strengthened.

Objective To investigate epidemical situation of drinking-tea fluomsis in Qinghai province, in order to understand diet structure to provide the scientific basis for the prevention and control and the scientific research. Methods In 2007, according to "Scheme for Survey on Epidemical Drinking-tea Fluorosis", we carried out an customized investigation in 28 counties, 3 townships sampled in each county, 2 villages in each township, 50 adults and 50 school-age children in each village; at same time, 1 monk temple was sampled in each county, 50 clergy adults and 50 children in each temple. Then we investigated the resident income, the diet structure, the brick tea consumption and so on, and applied Dean method to diagnose dental fluorosis. The patient number estimated based on the survey result. Results ①Yeady per capita income of people was mostly 500 - < 1000yuan, next 1000 - < 3000 yuan; economic income in pasturing area was higher than that of agriculture, half area and half agriculture and half pastoral region and township. ②Staple food was bread flour primarily in the animal husbandry agricultural half pastoral area,next were the roasted barley and the rice;the bread flour was the principle food in the agricultural region and the cities,next were the rice and the roasted barley;among non-staple food,meat came fimt and milk foHowed,egg the last.③The frequently edible vegetables Was potato.cabbage and greenpepper,eaten by a majority of people[62.82%(6497/10 343)];as for fruits,apple,pear and orange was primarily consumed,75.95%(7856/10 343)of people ate less than 10 times every month.④Sixty-one thousand nine hundred and ninety-nine residents were registered,153 335 kg ofbrick tea was consumed in villages and towns,2.47 kg per person;in 1001 monks investigated,4120 kg of brick tea was consumed every year,4.12 kg per person.⑤Detection rate of adult dental fluorosis in the villages and towns was 24.11%(2494/10 343),that of the children was 24.38% (3012/12 355);detection rate of dental fluorosis in monks was 26.13%(203/777),that of the children was 39.73% (89/224).⑥Detection rate of adult skeletal fluorosis in villages and towns was 15.60%(17/109);that of monks was 4.88%(2/41).⑦The 95%confidence limit estimated a total number of dental fluorosis patients were 1 084 306- 1 134 170 persons.the median Was 1 109 238 persons;the 95% confidence limit estimated a total number of skeletal fluorosis patients were 309 177-758 199 persons,the median was 533 688 persons.Conclusions Qinghai province has a great quantity of brick tea consumption,having lots of people with drinking-tea fluorosis which is in severe degree.The resident food structure was monotonous and mostly transpolted from other region.

OBJECTIVESTo elucidate the possible involvement of monoamine neurotransmitters in the development of neurobehavioral damage produced by acrylonitrile in drinking water in male rat brains.

METHODSTotally 30 male SD rats were randomly divided into three groups, the control group (n = 10), low dosage group (n = 10), and high dosage group (n = 10), which were respectively administered 0 mg/L, 50 mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for 12 weeks. Seven animals were randomly selected from each group for determination of monoamine neurotransmitters in striatum and cerebellum by high performance liquid chromatography with electrochemical detector and activities of monoamine oxidase in cortex.

RESULTSThe contents of dopamine in the striatum of low and high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet tissue, respectively, and compared with that of control group (9.0 +/- 4.2) microg/g wet tissue, the differences were statistically significant. There were no statistical differences among the contents of dopamine in the cerebellum of all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115 +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively and in low-dosage group they were significantly higher than those in other groups. There was dosage-dependently decreasing of the contents of serotonin of striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95) ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue.

CONCLUSIONThis study underlines the importance of alterations in the monoamine neurotransmitters system as a possible causative mechanism behind the behavioural and functional changes produced by acrylonitrile.

Acrylonitrile ; administration & dosage ; toxicity ; Animals ; Biogenic Monoamines ; metabolism ; Brain ; drug effects ; metabolism ; Carcinogens ; administration & dosage ; toxicity ; Cerebellum ; drug effects ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Corpus Striatum ; drug effects ; metabolism ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Drinking ; Male ; Neostriatum ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

To observe the antipyretic effect of Reduning injection (RDN) on lipopolysaccharide (LPS)-induced fever rats and its impact on centric fever medium. Rats were randomly divided into the blank control group, the model group, the Metamizole group, and high and low-dose RDN groups. Except for the blank control group, all of the rats were injected intraperitoneally with LPS (80 microg x kg(-1)) to observe their body temperature changes. The double-antibody sandwich ELSIA method was adopted to determine cAMP content in hypothalamus and MPO in lung tissues of fever peak rats. The high-dose RDN group can obviously reduce the temperature rise in fever rats, and cAMP and MPO content in hypothalamus. RDN showed significant antipyretic effect, which may be related with the reduction of cAMP content in hypothalamus and MPO in lung tissues.
Animals ; Antipyretics ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Fever ; chemically induced ; drug therapy ; Lipopolysaccharides ; Male ; Plants, Medicinal ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The aim of this study was to investigate the inhibition effect of arsenic sulfide (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTT, flow cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0-0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2) after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows no inhibition effect on proliferation of MDS cells; high concentration of As2S2 (1.5-50 mg/L) induces apoptosis of MDS cells.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Bone Marrow Cells ; pathology ; Cyclin D1 ; biosynthesis ; genetics ; Female ; Humans ; Leukocytes, Mononuclear ; pathology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Sulfides ; pharmacology ; bcl-2-Associated X Protein ; biosynthesis ; genetics

Objective To observe the state of endemic flurosis, construction and running status of water improvement projects in order to provide a scientific basis for prevention and treatment fluorosis. Methods Water samples of the diseased and nondiseased villeges were collected from east, west, south, north and centre of each villege in 2005, and fluoride concentration was determined for each surveyed village with unimproved-water. At the same time, all the tap water and source water samples were collected to determine fluoride concentration in each water-improved village surveyed. In 2008, all the endemic fluorosis villages in Guied county were divided into slight, medium and heavy types according to the water fluoride content before water improved, and 1,1,3 survey villages were chosen from each type. In all of the village children aged 8 to 12 years were tested for dental fluorosis by Dean method. Six copies of the urinary fluoride were sampled in different age groups. The fluorine content in water and urine was determined by F-ion selective electrode. The situation of clinical skeletal fluorosis of adults over 16 years of age was investigated, 20 adults (evenly divided between men and women) in the villages of medium and heavy types were examined by X-ray for skeletal fluorosis. Results In 3 village fluoride content of drinking water exceeded the national drinking water standards ( <1.0 mg/L) of 85 surveyed villages with improved-water. Among the 16 projects, 8 were intermittently running and 3 were retired, leaving only 31.25% of the projects active. Theprevalence of enamel fluorosis was 41.13%( 116/282), that of skeletal flurosis was 47.95%(969/2021) and that of X-ray checked was 20.73% (17/82). The median of urine fluoride was 1.06 mg/L and the scope was 0.20 - 9.44 mg/L.Conclusions Most of the improved-water projects do not normally supply water in the disease ward of Guide county. Therefore, there is an increasing trend of the disease, so further control measures are needed.

Objective To investigate the fulfillment of improved water measures for endemic fluomsis and to find out the trend of prevalence in Qinghai Province in order to provide scientific basis and technical support for the government to formulate control strategies for endemic fluorosis.Methods Usage and management of reforming water facilities in Huzhu County were generally surveyed.Yanya Village,Caijiabu Town,Huzhu County was chosen as the surveillance spot.The household drinking water was surveyed.The dental fluorosis and urine fluoride content of children aged 8-12 years and adult above 16 years were examined.Skeletal fluorosis of adult was checked.The fluomsis content in drinking water and urine was determined with F-ion selective electrode method.The dental fluowsis was examined with Dean index.Skeletal fluorosis was diagnosed according to eountry standard(GB 16396-1996.WS 192-1999).Results The rate of water-improving was 60%(36/60)in Huzhu County.The mean of fluoride content in drinking water Was 1.25 mg/L The prevalence rate of dental fluorosis of children aged 8-12 years was 90.20%(46/51);that of adult was 88.89%(48/54).The dental fluorosis index of children was 1.77,that of adult was 2.95.The prevalence rate of skeletal fluorosis was 98.15% indicated by clinical data,18.87% by X-ray.The ufine fluorosis content of children was 2.27 mg/L,that of adult was 2.00 mg/L.Conclusion The disease condition of endemic fluorosis in Qinshai is serious,defluofidation is slow in effect.