ABSTRACT
@#AIM: To observe changes in the flash electroretinogram(ERG)and retinal microcirculation in mice suspended by their tails, an animal model that simulates cephalad movement of bodily fluids under conditions of microgravity.<p>METHODS: Thirty-six adult male C57BL/6J mice(36 eyes)were randomly divided into three experimental groups and three control groups. Mice in the experimental groups were tail-suspended for 15d(Group one), tail-suspended for 30d(Group two), or tail-suspended followed by returning to normal position for 30d(Group three). Three control groups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60d. The mice were immediately examined using scotopic ERG(including oscillatory potentials \〖OPs\〗)and fundus fluorescein angiography(FFA)<i>in vivo</i>, and subsequently sacrificed to analyze the retinal histology(methods including immunohistochemistry and TUNEL staining)<i>in vitro</i>. Independent sample <i>t</i>-test was used for data comparison between the same time-point groups.<p>RESULTS: Following 15-days' tail-suspension, scotopic ERG showed a decline in OPs, but not in the b-wave; the second OP(O2)showed an amplitude of 197±33μV, which was about 60% of the control level(<i>t</i>=-5.938, <i>P</i><0.001). Following 30-days' tail-suspension, ERG recovered, with O2 showing an average value of 264±39μV; when compared to the corresponding control group(308±41μV), no significant difference was observed(<i>t</i>=-1.887, <i>P</i>>0.05). Morphologically, only the 15-days' tail-suspended mice showed FFA with microvascular dilation and tortuosity. Rhodopsin and cone-opsin were almost normal and no apoptotic-positive signals were detected in the retinas of the three tail-suspended groups.<p>CONCLUSION: Simulating cephalad shifting of bodily fluids as under microgravity, using short-term tail-suspension can affect rodent ERG and retinal microcirculation; however, the change is reversible with no obvious permanent injury observed in the retinas.
ABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between the polymorphism of butyrylcholinesterase (BChE, EC 3.1.1.8) and paraoxonase (PonE, EC 3.1.8.1), and the individuals' genetic susceptibility to organophosphates pesticides (OPs) exposure.</p><p><b>METHODS</b>75 OPs exposure workers were selected to determine their BChE-K, PON-192 and PON-55 genotypes using PCR-RFLP. The accumulative symptom scores and the whole blood acetylcholinesterase activity (mmol x h(-1) x ml(-1)) were used as health index. Firstly, the health condition related to single gene site of the three gene loci was analyzed to determine which kinds of genotype were susceptible. Then, used the multiple variance analysis was to see if there existed interactions among these three gene loci. Finally, established the multi-factor linear regression equation, in which considered some other factors that might influence the health situation such as age, gender and the exposure time. According to the equation, could get the accumulative symptom scores of each kind of subpopulation of different genotypes.</p><p><b>RESULTS</b>The mean AChE activities of the exposed workers with BChE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) were 105.0 +/- 23.0, 84.4 +/- 16.4, 79.0 +/- 9.9, respectively; The accumulative symptom scores were 3.7 +/- 3.8, 9.2 +/- 3.0, 12.5 +/- 0.7, respectively. The AChE activities of the exposed workers with PON-192 genotype BB (37 cases), genotype AB (27 cases) and genotype AA (11 cases) were 116.8 +/- 15.1, 91.2 +/- 15.6, 72.3 +/- 21.4, respectively; The accumulative symptom scores were 2.0 +/- 3.2, 6.7 +/- 3.3, 9.7 +/- 1.8, respectively. Similarly, the AChE activities of the exposed workers with PON-55 genotype LL (70 cases) and genotype LM (5 cases) were 102.4 +/- 23.0, 82.8 +/- 22.0; The accumulative symptom scores were 4.5 +/- 4.2, 9.2 +/- 3.6, respectively. Single variance analysis showed that the accumulative symptom scores of the individuals with abnormal homozygote of these three gene loci were the highest, which indicated that they were most susceptible to OPs. Multiple variance analysis showed there were no interactions among the three gene loci. Age, gender and exposure time had no statistical significance, while genotypes of the three gene loci had statistical significance to health situation.</p><p><b>CONCLUSION</b>Genotypes of BChE-K, PON-192 and PON-55 are related to susceptibility to OPs exposure.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Aryldialkylphosphatase , Genetics , Butyrylcholinesterase , Genetics , Genetic Predisposition to Disease , Genotype , Occupational Exposure , Organophosphorus Compounds , Pesticides , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment LengthABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect of memantine on the regulation of N-methyl-D-aspartate (NMDA) receptor in dichlorvos-poisoned rat brain, and to understand the mechanism of its role in organophosphate poisoning.</p><p><b>METHODS</b>SD rats were administrated dichlorvos (25 mg/kg, ip) then three groups were treated with memantine at doses of 5, 15 and 45 mg/kg respectively. The activity of acetylcholinesterase (AChE) and binding capacity of NMDA receptor with [(3)H]MK-801 were determined 16 h after dichlorvos injection.</p><p><b>RESULTS</b>The time of onset of toxic symptoms in 15, 45 mg memantine treated groups [(18.40 +/- 1.14) and (21.40 +/- 1.52) min respectively] was higher than that in dichlorvos alone group [(16.75 +/- 1.62) min]; the intensity of muscle fasciculation (1.60 +/- 1.14 and 0.80 +/- 0.84, respectively) was less than that in control group (2.85 +/- 0.37); the total score of poisoning symptoms (8.80 +/- 1.79 and 9.00 +/- 2.24 respectively) was also less than that in dichlorvos group (14.60 +/- 1.70). The AChE activities both in blood and brain of memantine treated groups were not significantly different from those in dichlorvos alone group. The affinity (Kd value) and density (Bmax value) of brain NMDA receptor in dichlorvos exposed rats [(75.55 +/- 7.87) nmol/L, (0.46 +/- 0.06) pmol/mg pro respectively] were higher and lower respectively than those in control group [(37.37 +/- 4.17) nmol/L, (0.62 +/- 0.04) pmol/mg pro respectively]. Lower level of memantine (5 and 25 mg/kg) could antagonize the dichlorvos-evoked down-regulation of [(3)H]MK-801 binding to NMDA receptor in rat brain [Bmax value: (0.55 +/- 0.07) and (0.64 +/- 0.07) pmol/mg pro; Kd value: (38.68 +/- 4.54) and (32.58 +/- 3.90) nmol/L respectively] while higher dose of memantine (45 mg/kg), the Bmax (0.45 +/- 0.06) pmol/mg pro and Kd (22.88 +/- 4.42) nmol/L of NMDA receptor were significantly decreased (P < 0.01).</p><p><b>CONCLUSION</b>Memantine in certain dose range could protect against the down-regulation of NMDA receptor in rat brain, and alleviate organophosphorus poisoning symptoms to some extent. The recovery of AChE activity inhibition wasn't involved in the treatment with memantine on dichlorvos poisoning, therefore, atropine and a proper AChE reactivator (an oxime) should be used clinically.</p>