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.

To explore the mechanism of Fuyang Jiebiao granules against viral pneumonia based on network pharmacology and pharmacodynamics

Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.

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.

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.

Short Term Effect of 0.02%/0.04% Atropine Sulfate Eye Drops on Choroid Thickness in Children with Myopia

Objective: Short-term effects of 0.02%/0.04% atropine sulfate eye drops on choroidal thickness in myopic children using optical coherence tomography angiography. Methods: Thirty-two children aged 6 - 12 years were selected and divided into 22 cases and 44 eyes in the 0.02%/0.04% atropine sulfate eye drops observation group and 10 cases and 20 eyes in the control group. The linear regression equation was used to evaluate the correlation among the spherical equivalent, the axial length and the subfoveal choroidal thickness, moreover, used to evaluate the correlation between the baseline and 6 months later. Independent samples T-test was used to detect whether there was any statistical difference between the nasal 1 mm subfoveal choroidal thickness and the temporal 1 mm subfoveal choroidal, meanwhile, compared with the baseline and 6 months later. P Results: After 6 months follow-up, the axial length increased by 0.067 ± 0.199 mm in the atropine group, 0.201 ± 0.081 mm in the control group (P Conclusions: 1) 0.02%/0.04% atropine sulfate eye drops can delay the growth of axial length and spherical equivalent;2) 0.02%/0.04% atropine sulfate eye drops can thicken the choroid, and the thickness of the nasal side 1mm is the same as that of the temporal side 1 mm;3) At baseline, the subfoveal choroidal thickness has no significant correlation with the axial length and spherical equivalent;4) After 6 months, changes in axial length and spherical equivalent were negatively correlated with changes in subfoveal choroidal thickness.

0.05% atropine on control of myopia progression in Chinese school children: a randomized 3-year clinical trial

·AIM:To evaluate the effect of 0.05%atropine on the control of myopia for 2y(phase I)and on spherical equivalent refraction(SER)progression for 1y(phase II)after its withdrawal in Chinese myopic children.·METHODS:Totally 142 children with myopia were randomly assigned to the 0.05%atropine group or to the placebo group.In phase I,children received 1 treatment for each eye daily.In phase II,the patients received no treatment.Axial length(AL),SER,intraocular pressure(IOP)and atropine-related side effects were assessed at 6 months’intervals.·RESULTS:During phase I,the mean change of SER was-0.46±0.30 D in the atropine group,compared to-1.72±1.12 D in the placebo group(P<0.001).The mean change of AL in the atropine group(0.26±0.30 mm)was significantly shorter than that in the placebo group(0.76±0.62 mm,P=0.002).In addition,in phase II(12mo after the withdrawal of atropine),there was no significant difference in AL change from the atropine group,when compared with that from the placebo group(0.31±0.25 mm vs 0.28±0.26 mm,P>0.05).Furthermore,the change in SER from the atropine group was 0.50±0.41 D,which was significantly lower than 0.72±0.60 D from placebo group,(P<0.05).Finally,there were no statistically significant differences in IOP between the treatment and control groups at any stages(all P>0.05).·CONCLUSION:The use of 0.05%atropine for two consecutive years may effectively control elongation of AL and thus progression of myopia,without significant SER progression 1y after atropine withdrawal.Therefore,treatment with 0.05%atropine daily for 2y is effective and safe.

Anorectal Pharmacodynamics and In Vitro Drug Release of Clerodendrum bungei Steud.Extract Gel

[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.

Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole

BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.

Pharmacodynamic Study of Parallel Groups Comparing the Effect of Rivaroxaban 20 Mg (Laboratorios Leti, S.A.V.) vs Rivaroxaban 20 Mg (Bayer Laboratories) on Prothrombin Time

Background: The prevalence of both atrial fibrillation (FA) and diabetes mellitus (DM) is increasing and they often occur together and constitute a high risk of thrombosis. Rivaroxaban is a Factor Xa inhibitor with a rapid onset and disappearance of action after oral administration;it acts by inhibiting the active form of the coagulation factor. In order to reflect the effect of the action of Rivaroxaban, we used the prothrombin time (PT);however, it′s not the most accurate, but it is the one available in our community. Methods: This was a prospective, randomized, analyst-blinded, parallel group clinical study to verify the efficacy of Rivaroxaban Leti 20 mg (RL) (12 volunteers vs Rivaroxaban Bayer 20 mg (RB) (13 volunteers). The variables were determination of PT and Partial Thromboplastin Time (aPTT) at baseline and at 24, 48 and 72 hours after administering a daily dose of 20 mg for three days. The determination was carried out with the IDG method (Integrated Diagnostics Group Sanzay Corporation) with an International Sensitivity Index (ISI) of 1.17 PT and aPTT were taken before the first dose, and then, every day during the next 3 days, three hours after the ingestion of their daily dose at 7 am. Results: The 25 healthy volunteers were similar in age, BMI, and SBP/DBP level with a greater number of men in the Bayer group. The efficacy of rivaroxaban was similar in both groups with prolongation of PTT to the 2nd day of treatment with PT, and percentage changes from baseline (14.46 ± 0.97 for RB vs 14.17 ± 0.94 RL p: 0.45), PTT results and percentage changes from the base (RB: 34 ± 4.53 RL: 33.46 ± 2.82). The safety of rivaroxaban was good in both groups with no serious adverse events. The equivalence in the logarithmically transformed PT result (ln) on day two, Mean and CI (90%) 99.2 (94.4-104) and 100 (99.5-100.8);neither the means nor the 90% confidence intervals of the PT variable transformed logarithmically to ensure its normality, were far from the 80%-125% allowed for declaration of similarity. Conclusion: The test formulation Rivaroxaban Asarap? 20 mg, manufactured by Leti Laboratories, is interchangeable or bioequivalent in clinical and laboratory response to the reference formulation Xarelto? manufactured by Bayer Laboratories.

Advances in Research Methods of Pharmacodynamic Substances in Traditional Chinese Medicines and Their Application in the Teaching of Traditional Chinese Medicine Analysi

With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.

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.

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.

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.

Individualized immunosuppression: new strategies from pharmacokinetics,pharmacodynamics and pharmacogenomics

The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient's immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians. DATA SOURCES:The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors. RESULTS:Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly-used im- munosuppressants. Recent progress in study of pharmaco-kinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM). CONCLUSIONS:Individualizing organ recipient's immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.

Pharmacokinetics and pharmacodynamics of lignocaine: A review

Lignocaine is an essential drug on World Health Organisation essential drug list, considered efficacious, safe and cost-effective for any health-care system. Despite its ubiquitous use in medicine and surgery, there are few detailed reviews of its pharmacokinetics and pharmacodynamics. Being an amide-type local anesthetic and Class 1b antiarrhythmic, lignocaine is most frequently used clinically for its anesthetic and antiarrhythmic benefits. However, lignocaine has important antinociceptive, immuno-modulating, and antiinflammatory properties. Information pertaining to the pharmacokinetics and pharmacodynamics of lignocaine was examined by performing a literature search of Pub Med, Embase and MEDLINE(via Ovid), pharmacology textbooks and online sources. We present a focused synopsis of lignocaine's pharmacological composition, indications for use and mechanisms of action, focusing on its anti-inflammatory, immuno-modulating and analgesia effects. In addition we review the dosing regimes and infusion kinetics of lignocaine in the clinical setting. Finally, we review the evidence for ligocaine's modulation of the inflammatory response during major surgery and its specific effects on cancer recurrence. These indirect effects of local anesthetics in tumor development may stem from the reduction of neuroendocrine responses to the stress response elicited by major surgery and tissue damage, enhanced preservation of immune-competence, in addition to opioid-sparing effects of modulating tumor growth.

VENTRICAL MICROINJECTING ATROPINE OR NALOXONE REDUCES ANALGESIC EFFECTS PRODUCED BY BRAIN STIMULATION IN THE RAT

Stimulating SmI cortex like needling points produced analgesic effect in rats.Under the background of ventrical microinjecting atropine（10μg/2μl）or naloxone（20μg/20μl）tailflick latency（TEL）remained unchanged after stimulating SmI.Comparing atropine group or naloxone group with normal saline group it was shown that there were a statistical difference in TFL between the two groups respectively.Thus,both ACh and endogenous morphine-like factors may participate in analgesic effect as a neurotransmitter of the corticofugal modulation of pain.

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.

Objectively-measured compliance to atropine penalization treatment in children with amblyopia: a pilot study

Background:To date,compliance to atropine penalization in amblyopic children has only been assessed through self-report.The goal of this pilot study is to measure compliance to atropine penalization objectively.Methods:Seven amblyopic children(3-8 years;20/40-20/125 in the amblyopic eye) were enrolled.None had been treated with atropine previously.Children were prescribed either a twice per week or daily atropine regimen by their physicians.Compliance was defined as the percentage of days in which the atropine eye drop was taken compared to the number of doses prescribed.We used medication event monitoring system(MEMS) caps to objectively measure compliance.The MEMS caps are designed to electronically record the time and date when the bottle is opened.The parents of the children were provided a calendar log to subjectively report compliance.Participants were scheduled for return visits at 4 and 12 weeks.Weekly compliance was analyzed.Results:At 4 weeks,objective compliance averaged 88%(range,57-100%),while subjective compliance was 98%(range,90-100%).The actual dose in grams and visual acuity(VA) response relationship(r=0.79,P=0.03) was significantly better than the relationship between regimen and response(r=0.41,P>0.05),or the relationship between actual dose in drops and response(r=0.52,P>0.05).Conclusions:Objective compliance to atropine penalization instructions can be monitored with MEMS,which may facilitate our understanding of the dose-response relationship.Objective compliance with atropine penalization decreases over time and varies with regimen.On average,subjective parental reporting of compliance is overestimated.

Evaluation of pharmacokinetics and pharmacodynamics relationships for Salvianolic Acid B micro-porous osmotic pump pellets in angina pectoris rabbit

The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max) was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.