The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Metaanalysis

AIM:To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia.METHODS:A systematic search was conducted across the Cochrane Library,PubMed,Web of Science,EMBASE,CNKI,CBM,VIP,and Wanfang database,encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17,2024.Data extraction and quality assessment were performed,and a network Meta-analysis was executed using Stata version 14.0 Software.Results were visually represented through graphs.RESULTS:Fourteen papers comprising 2475 cases were included;five different concentrations of atropine solution were used.The network Meta-analysis,along with the surface under the cumulative ranking curve(SUCRA),showed that 1%atropine(100%)>0.05%atropine(74.9%)>0.025%atropine(51.6%)>0.02%atropine(47.9%)>0.01%atropine(25.6%)>control in refraction change and 1%atropine(98.7%)>0.05%atropine(70.4%)>0.02%atropine(61.4%)>0.025%atropine(42%)>0.01%atropine(27.4%)>control in axial length(AL)change.CONCLUSION:In Chinese children and teenagers,the five various concentrations of atropine can reduce the progression of myopia.Although the network Meta-analysis showed that 1%atropine is the best one for controlling refraction and AL change,there is a high incidence of adverse effects with the use of 1%atropine.Therefore,we suggest that 0.05%atropine is optimal for Chinese children to slow myopia progression.

Atropine can induce autophagy independent of the M3 muscarinic acetylcholine receptor

Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.

Evaluation of the clinical effects of atropine in combination with remifentanil in children undergoing surgery for acute appendicitis

BACKGROUND Acute appendicitis(AA)is the most common cause of acute abdomen in children.Anesthesia significantly influences the surgical treatment of AA in children,making the scientific and effective selection of anesthetics crucial.AIM To assess the clinical effect of atropine(ATR)in combination with remifentanil(REMI)in children undergoing surgery for AA.METHODS In total,108 cases of pediatric AA treated between May 2020 and May 2023 were selected,58 of which received ATR+REMI[research group(RG)]and 50 who received REMI[control group(CG)].Comparative analyses were conducted on the time to loss of eyelash reflex,pain resolution time,recovery time from anesthesia,incidence of adverse events(AEs;respiratory depression,hypoxemia,bradycardia,nausea and vomiting,and hypotension),intraoperative responses(head shaking,limb activity,orientation recovery,safe departure time from the operating room),hemodynamic parameters[oxygen saturation(SPO2),mean arterial pressure,heart rate,and respiratory rate],postoperative sedation score(Ramsay score),and pain level[the Face,Legs,Activity,Cry,Consolability(FLACC)Behavioral Scale].RESULTS Compared with the CG,the RG showed significantly shorter time to loss of eyelash reflex,pain resolution,recovery from anesthesia,and safe departure from the operating room.Furthermore,the incidence rates of overall AEs(head shaking,limb activity,etc.)were lower,and influences on intraoperative hemodynamic parameters and stress response indexes were fewer.The Ramsay score at 30 min after extubation and the FLACC score at 60 min after extubation were significantly lower in the RG than in the CG.CONCLUSION ATR+REMI is superior to REMI alone in children undergoing AA surgery,with a lower incidence of AEs,fewer influences on hemodynamics and stress responses,and better post-anesthesia recovery.

Analgesic effects of receptin, a chemically modified cobratoxin from Thai-land cobra venom

Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally （5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.） or intra-cerebral venticularly （62.5 μg/kg, i.c.v.）. The antinociceptive action was determined using the hotlate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine （Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.） or naloxone （Nal; 3 mg/kg, i.p.）. The effect of REC on motor activity was tested using the Animex test in mice. Results REC （5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.） exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 μg/kg （1/160 of systemic dose; i.c.v.）produced marked analgesic effects. Atropine at 0.5 mg/kg （i.m.）, 10 mg/kg （i.p.） or naloxone at 3 mg/kg （i.p.） failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC＇s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.

Effect of Co-administration of Morphine and Cholinergic Antagonists on Y-maze Spatial Recognition Memory Retrieval and Locomotor Activity in Mice

The interaction of morphine and cholinergic system was shown in previous studies. In the present study, we investigated whether morphine would interact with the cholinergic antagonists, scopolamine and atropine in a Y-maze spatial recognition memory. Pre-test treatments of morphine （5, 1.5, 0.5 mg/kg）, scopolamine （1, 0.1 mg/kg）, atropine （0.5, 0.1 mg/kg） were used in the experiments, relatively high or low doses were paired respectively as co-administration measures. The results showed that co-administration of morphine 0.Smg/kg ~ scopolamine 0.1 mg/kg and morphine 0.5 mg/kg ＋ atropine 0.1 mg/kg disturbed the inspective exploratory behavior （percent of arm duration） but not the inquisitive behavior （percent of arm visits） of the spatial memory retrieval, while the drugs didn＇t cause amnesia when single administered of the concerned low doses. Distinct interaction was found between scopolamine and morphine on increasing locomotor activity.

Antagonism of 3-(2',2',2'-Phenyl-cyclopentyl-hydroxylethoxy)-quinuclidine Against the Depression of Respiratory Center Induced by Dichlorvos(DDVP)

以乌拉坦麻醉猫膈神经放电及肋间外肌放电为指标(可分别反映延髓呼吸中枢背侧组 DRG 和腹外侧组 VRG 的活动),观察3-(2′,2′,2′-苯基环戊基羟基乙氧基奎宁环(PCHE)对抗敌敌畏(DDVP)的呼吸中枢抑制作用,椎动脉(iva)注射 DDVP 2 mg,膈神经放电立即被抑制,继之肋间外肌放电也抑制或先短暂兴奋再抑制。再于椎动脉注射阿托品0.2 mg,仅少数动物(1/3)的肋间外肌放电开始恢复,当加大剂量至0.25 mg 时,部分动物的两种放电才恢复(2/6)。注射 PCHE 0.2mg,可使大部分动物(5/6)的两种放电同时恢复。提示DDVP 优势影响 DRG,阿托品对 VRG 的作用要比 DRG 明显,PCHE 对 DRG 及 VRG 均有较强的作用;PCHE 在低于阿托品剂量就可产生更强的对抗 DDVP 所致的呼吸中枢抑制作用。

The diluted atropine for inhibition of myopia progression in Korean children

AIM：To evaluate the efficacy and safety of three different concentrations of diluted atropine for the control of myopia in Korean children,and to assess the risk factors associated with rapid myopia progression.METHODS：A total of 285 children,with refractive errors within the range of-6 diopters（D）between 5 and 14 years of age were included.After using 0.01%,or 0.025%,or 0.05% atropine,for about 1y,changes in refraction,axial lengths and frequency of adverse events were analyzed.Logistic regression analyses were performed to evaluate the risk factors associated with rapid myopia progression.RESULTS：The changes in the mean spherical equivalent values were -0.134 D/mo in the before atropine group,-0.070 D/mo in the 0.01% atropine group,-0.047 D/mo in the 0.025% atropine group,and -0.019 D/mo in the 0.05% atropine group,with significant differences between the groups（P〈0.001）.The axial elongation was 0.046 mm/mo,0.037 mm/mo,0.025 mm/mo,and 0.019 mm/mo respectively,with significant differences between the groups（P=0.003）.The incidence of photophobia and near vision difficulty was not different among the three atropine groups（P=0.425and P=0.356,respectively）.Multivariate logistic regression analyses showed that only highly myopic parents were a significant predictive factor of rapid myopia progression in Korean children（odds ratio,8.155;95% confidence interval,3.626-18.342;P〈0.001）.CONCLUSION：Treatment with 0.01%,0.025% and 0.05% atropine solution inhibits myopia progression in Korean children in a dose-dependent manner.Children with highly myopic parents preferentially shows a rapid myopia progression rate.

Atropine 0.01% eye drops slow myopia progression: a systematic review and Meta-analysis

AIM: To evaluate the effects of atropine 0.01% on slowing myopia progression. METHODS: We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey(System for Information on Grey Literature in Europe), the ISRCTN registry, Clinical Trials.gov, and the WHO International Clinical Trials Registry Platform(ICTRP) from the dates of inception to June 30, 2018. RESULTS: Seven randomized controlled trials(RCTs) with a total of 1079 subjects were included(505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group (MD=-0.12, 95%CI(-0.19,-0.06))There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI(-0.25,-0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure (MD=0.08, 95%CI(-0.27, 0.42);MD=0.09, 95%CI(-0.17, 0.36);MD=-0.01, 95%CI(-0.02, 0.00);MD=0.08, 95%CI(-0.56,0.40))The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups (OR=0.26, 95%CI(0.11, 0.61))CONCLUSION: Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.

Effect of areca on contraction of colonic muscle strips in rats

AIM: To investigate the effects of areca on the contractile activity of isolated colonic muscle strips in rats and mechanism involved. METHODS: Each strip (LMPC, longitudinal muscle of proximal colon; CMPC, circular muscle of proximal colon; LMDC, longitudinal muscle of distal colon; CMDC, circular muscle of distal colon.) was suspended in a tissue chamber containing 5 mL Krebs solution (37 degrees C), bubbled continuously with 950 mL.L(-1) O(2) and 50 mL.L(-1) CO(2). The mean contractile amplitude (A), the resting tension (T), and the contractile frequency (F) were simultaneously recorded on recorders. RESULTS: Areca dose dependently increased the mean contractile amplitude, the resting tension of proximal and distal colonic smooth muscle strips in rats (P【0.05). It also partly increased the contractile frequency of colonic smooth muscle strips in rats (P【0.05). The effects were partly inhibited by atropine (the resting tension of LMPC decreased from 0.44 +/- 0.12 to 0.17 +/- 0.03; the resting tension of LMDC decreased from 0.71 +/- 0.14 to 0.03 +/- 0.01; the mean contractile amplitude of LMPC increased from -45.8 +/- 7.2 to -30.5 +/- 2.9; the motility index of CMDC decreased from 86.6 +/- 17.3 to 32.8 +/- 9.3; P【0.05 vs areca), but the effects were not inhibited by hexamethonium (P】0.05). CONCLUSION: Areca stimulated the motility of isolated colonic smooth muscle strips in rats. The stimulation of areca might be relevant with M receptor partly.

Review on current concepts of myopia and its control strategies

Myopia poses a significant burden on the healthcare system,economy and quality of life.It is an emerging global public health challenge and requires interventions to delay or stop onset and progression.With changing times and evidence,the concepts of myopia are changing along with the treatment and control strategies.Behavioural modifications including increased outdoors time and reduced near work,optical and pharmaceutical management options are reviewed.This paper presents a current overview on the concepts of myopia,and is expected to summarize updates on myopia control methods.

A short-chain α-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia

Objective To investigate the analgesia induced by cobrotoxin （CT） from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally （33.3, 50, 75 μg/kg）, intra-cerebral venticularly （2.4 μg/kg） or microinjected into periaqueductal gray （PAG, 1.2 μg/kg）. The antinociceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine （0.5 mg/kg, im or 10 mg/kg, ip） or naloxone （3 mg/kg, ip）. The effect of CT on motor activity was tested using the Animex test. Results CT （33.3, 50 and 75 μg/kg, ip） exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 μg/kg （1/23th of a systemic dose） produced marked analgesic effects. Microinjection of CT 1.2 μg/kg （1/46th of systemic dose） into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg （ira） or naloxone at 3 mg/kg （ip） failed to block the analgesic effects of CT, but atropine at 10 mg/kg （ip） did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception （75 μg/kg）, CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT＇ analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

Effect of morphine and M-cholinoceptor blocking drugs on human sphincter of Oddi during choledochofiberscopy manometry

OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly. RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly. CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.

Antidiarrheal activity of Pterocarpus erinaceus methanol leaf extract in experimentally-induced diarrhea

Objective:To investigate the antidiarrheal activity of the methanol leaf extract of Pterocarpus erinaceus in vivo.Methods:The methanol leaf extract of Ptemcarpus erinaceus was evaluated using different doses(100,200 and 400 mg/kg body weight) orally for antidiarrheal activity using castor oil-induced diarrhea,charcoal meal transit lime and castor oil-induced enteropooling in different groups of albino Wistar mice.The activity of the extract at different doses were compared to diphenoxylate(3 mg/kg) and atropine sulphate(3 mg/kg) which were used as standard reference drugs and also to the distilled water administered negative control group of mice.Results:The extract at the doses used caused a significant(P【 0.01) reduction in the wet faeces passed by the mice in the castor oil-induced diarrhea,decreased the distance travelled by the charcoal meal by up to 54.8%and also caused a dose dependent and significant(P【 0.001) reduction in the intraluminal fluid accumulation in the castor oil-induced enteropooling. Conclusions:Our results indicate that Pterocarpits erinaceus extract produced significant antidiarrheal activity and the action may attribute to inhibition of gastrointestinal movement and fluid secretion.

Choroidal thickness,myopia,and myopia control interventions in children:a Meta-analysis and systemic review

AIM:To investigate changes of choroidal thickness(ChT) in children with myopia and the effect of current myopia control interventions on ChT.METHODS:Major literature databases were searched for studies relevant to myopia in children.All studies used swept-source optical coherence tomography(SS-OCT) or enhanced depth imaging optical coherence tomography(EDI-OCT) to measure the ChT value.The weighted mean difference(WMD) and 95% confidence interval(CI) were pooled to evaluate ChT in myopia children.RESULTS:A total of 11 eligible articles,including 1693 myopic and 1132 non-myopic eyes,were included in the first Meta-analysis.The sub-foveal choroidal thickness(SFCT;WMD=-40.06,95%CI,-59.36 to-20.75,P<0.001) and ChT at other sectors were significantly thinner in myopic eyes compared with the non-myopic eyes.The Meta-analysis revealed that the ChT decreased horizontally from the temporal sector toward the nasal sector in the pediatric myopia population.Another 11 studies reporting the effect of myopia control interventions were included in the second Meta-analysis for the relationship between myopia control treatments and ChT.SFCT significantly increased after orthokeratology(OK) treatment and OK combined with 0.01% atropine(OKA) treatment(WMD=19.47,95%CI,15.96 to 22.98,P<0.001;WMD=21.81,95%CI,12.92 to 29.70,P<0.001,respectively).The forest plots showed that SFCT changed little in myopic children receiving 0.01% atropine(P=0.30).Furthermore,the Meta-analysis showed that OK treatment had a stronger effect on the value of SFCT in myopic children as compared with 0.01% atropine(WMD=9.86;95%CI,-0.21 to 19.93,P=0.05).There is no difference between the treatment with OK and OKA treatment in ChT in myopic children(P=0.37).CONCLUSION:The ChT in myopic eyes is thinner than that in non-myopic eyes in pediatric population.Myopia control interventions including OK and OKA lead to ChT thickening,but other treatments such as 0.01% atropine did not show an increase in ChT.

Efficacy and safety of atropine at different concentrations in prevention of myopia progression in Asian children: a systematic review and Meta-analysis of randomized clinical trials

AIM:To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children.METHODS:Databases(PubMed,EMBASE,the Cochrane Library and Web of science)were comprehensively searched from inception to April 2022.Types of studies included were randomized clinical trials(RCTs).The published languages were limited to English.Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions.Funnel plots and Egger’s test were used for detection of publication bias.Meta-analyses were conducted using STATA(version 15.0;StataCorp).RESULTS:A total of 15 RCTs involving 2268 patients were included in the study.In the atropine group,spherical equivalent progressed at a significantly lower rate[weighted mean difference(WMD)=0.39,95%confidence interval(CI):0.23,0.54]than in the control group.A WMD of 0.15 mm was associated with less axial elongation(95%CI-0.19,-0.10).Different doses showed statistically significant differences(P<0.05)and an improved effect could result from a higher concentration.Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm(95%CI:0.33,1.06)and 0.38 mm(95%CI:0.22,0.54)more than the control group.In the present Meta-analysis,no changes in accommodative amplitude(AA)were associated with atropine administration.Atropine administration increased the risk of adverse effects by 1.37 times.CONCLUSION:Concentrations of less than 1%atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner.Meanwhile,it caused pupil enlargement,but induced no change in the AA within this range.Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.

Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate

Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p < 0.001), and versus basal production( p < 0.001). TBUT showed statistically significant differences between groups(days 3 and 10;p = 0.001) and versus basal values(day 3;p < 0.001). Fluorescein staining showed a statistically significant difference(day 3;p = 0.001). The most frequent clinical finding was conjunctival hyperemia(76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation(86.7% minimal;13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.Conclusions : The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.

Effect of muscarinic blocker on enhancing action of fructus aurantilii immaturus in the intestinal myoelectric activity in dogs

AIM To investigate the effect of Fructus Aurantii Immaturus (FAI) on the small intestinal electric activity. METHODS Effect of FAI was observed by using the computerized electrophysiologic method with migrating myoelectric complex (MMC) as a criterion. 100% FAI concentrated solution was given to fasted, healthy and conscious dogs by gastrostogavage, and as soon as the effect on electric activity of small intestine appeared, atropine was injected intramuscularly. RESULTS The enhancing action of FAI could be inhibited significantly by atropine, an antagonist of cholinergic receptor. It is shown that both the number of spike burst per cluster and the number of spike per minute in the phase Ⅱ and Ⅲ and general cycle were decreased ( P <0 01) although the duration of phase Ⅱ and general cycle were prolonged. CONCLUSION The effect of FAI might be related to muscarinic receptor.

Effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization in high myopia mice

AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization(CNV)in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk,and the high myopia was diagnosed by optometry,the diopter was less than-6.00 D,and CNV was induced by 532 nm laser.The changes of dopamine D1 receptor(DRD1),dopamine D2 receptor(DRD2),and vascular endothelial growth factor A(VEGFA)were detected by Western blot technology at 0.5,1,2h,and 7d after 0.01%,0.05%,and 0.1%atropine eye drops,respectively,the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5,1,2h,7d with 0.05%and 0.1%atropine eye drops(P<0.05).The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group,and the higher the concentration,the more significant the inhibitory effect(P<0.05).CONCLUSION:The 0.01%,0.05%,0.1%atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1,and the effect of 0.05%and 0.1%atropine eye drops is more significant.

Effects of acetylcholine injection on electric activities of pain-related neurons in the locus ceruleus of healthy rats

BACKGROUND： A large number of investigations have shown that acetylcholine （ACh） and the nucleus locus coeruleus （LC） play an important role in the modulation of pain in rats; however, there is no concrete evidence addressing the relationship between ACh injection into the LC and the electrical activities of pain-related neurons in the LC of healthy rats. OBJECTIVE： To study changes in the discharge of pain-related neurons in the LC following injection of ACh, or its M receptor antagonist, atropine, and to investigate the role of ACh and the LC in the pain signaling pathway. DESIGN, TIME AND SETTING： A randomized, controlled, neuroelectrophysiological animal experiment was performed from November 2007 to December 2008, in the Physiological Laboratory of Harbin Medical University, China. MATERIALS： Acetylcholine chloride was obtained from Shanghai San＇aisi Reagent Co., Ltd., China atropine was purchased from Tianjin Jinyao Amino Acid Co., Ltd., China. METHODS： This study was divided into two sections as follows： （1） 46 adult Wistar rats were randomly assigned into an ACh group and a control group, with 23 rats in each. （2） 34 adult Wistar rats were randomly assigned to an atropine group and a control group, with 17 rats in each. The sciatic nerve was stimulated by a series of electrical impulses, serving as peripheral noxious stimuli. Electrical changes in pain-related neurons in the LC were measured by glass microelectrodes. The LC of rats in the ACh and atropine groups were injected with 2 μg/μL ACh or 0.5 μg/μL atropine, respectively, in 1 μL volume. Rats in the control groups received injection of 1 pL physiological saline within 4 minutes. MAIN OUTCOME MEASURES： To measure the net increase in the discharge value, latency and complete inhibitory duration of pain-related neurons before and after administration of ACh or atropine. RESULTS： The injection of ACh into the LC increased the pain-evoked discharge frequency and shortened the latency of the pain-excitation neurons. It decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of pain-inhibition neurons. Injection of atropine into LC blocked the effects of ACh. CONCLUSION： ACh strengthened the response of pain-related neurons in LC of rats to noxious stimulation, exhibiting the effects of facilitated pain. This indicates that ACh and LC play an important role in the modulation of algesia.

Luminal oxidants selectively modulate electrogenic ion transport in rat colon

AIM： To investigate the effects of luminal exposure to H2O2 and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches. METHODS： Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe （FITC）. RESULTS： Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O2, except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O2. However, the Ca^2＋- activated response remained unchanged. CONCLUSION： H2O2 may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemiareperfusion by multiple mechanisms.