Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia

AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study.A total of 72 small-angle AACE patients received BTXA extraocular muscle injection.Patients were grouped by onset-to-treatment time(Group A:≤6mo,Group B:>6mo).Deviation of esotropia,eye alignment and stereopsis were analyzed at the period of pre/post-injection(1wk,1,3,and 6mo).Orthophoria rate at 6mo(horizontal deviation<10Δand binocular single vision)were considered as outcome index.RESULTS:There were no significant baseline differences(P>0.05)between two groups except onset-to-treatment time(2mo vs 11mo,P<0.001).Higher orthophoria rates were in Group A at last follow-up(94.74%vs 73.53%,P=0.013).Post-BTXA deviations of two groups at 1mo showed no difference(P>0.05);while in 3 and 6mo Group A was significantly smaller than group B(all P<0.001).No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A.In Group B,deviation at 3mo(near:2Δvs 0,P<0.001;distance:4Δvs 0,P<0.001)and 6mo(near:6Δvs 0,P<0.001;distance:6Δvs 0,P<0.001)was significant increased compared to deviation at 1wk after treatment.Group A showed better stereopsis recovery in last follow-up compared to Group B(80″vs 200″,P=0.002).Both groups obtained improved stereopsis after treatment(Group A:80″vs 300″,P<0.001;Group B:200″vs 300″,P=0.037).CONCLUSION:BTXA is effective for AACE with small deviation(≤25Δ)in early stage.Delayed treatment(>6mo)may reduce BTXA efficacy.Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Betulinic acid protects against ovarian impairment by decreasing F-2 toxin-induced oxidative stress and inflammation associated with the downregulation of p38 expression in mice

F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage.We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth,reducing inflammatory cell infiltration,repairing damaged mitochondria and endoplasmic reticulum.Simultaneously,BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels in the serum,but also restrained the protein expression of the estrogen receptors a(ERa)and ERβ.Moreover,BA restored the balance of F-2 toxin-induced ovarian redox system disorders.Subsequently,we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β(IL-1β).IL-6,and tumor necrosis factor-α(TNF-α)mRNA expression,as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression,which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.

Clinical effect of botulinum toxin type A combined with autologous fat grafting in patients with nasolabial fold depression

BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin A(BTX-A)injection(AFG+BTX-A injection)has been gradually applied in the treatment of patients with NLF depression.Although studies have been conducted on the efficacy and safety of AFG+BTX-A injection in treating NLF depression,the experimental design,observational indicators,and sample enrollment criteria vary remarkably,making it difficult to draw convincing and consistent conclusions.Thus,further relevant research is warranted.AIM To assess the esthetic improvement,efficacy,and safety of AFG+BTX-A injections in patients with NLF depression.METHODS This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021.These patients were categorized into control(n=30)and observation(n=30)groups.The observation group received AFG+BTX-A injection,whereas the control group underwent AFG only.All patients were evaluated using the wrinkle severity rating scale(WSRS)and global aesthetic improvement scale.The compactness of facial contours,skin evaluation indexes,adverse reactions,and satisfaction of the two groups were evaluated 3 months postoperatively.RESULTS The WSRS scores of the observation group at 1,3,and 6 months postoperatively were lower than those of the control group(P<0.05).Three months postoperatively,facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group(P<0.05).The compactness of facial contours was better in the observation group than in the control group(P<0.05).In addition,no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness,facial asymmetry,facial bruising,and facial concavity inequality(P>0.05).CONCLUSION AFG+BTX-A injection is a highly safe,cost-effective,effective,and long-lasting treatment for NLF depression with high esthetic value,which should be promoted in the future.

Botulinum toxin type A injection combined with biofeedback in the treatment of spastic pelvic floor syndrome

BACKGROUND Spastic pelvic floor syndrome(SPFS)is a refractory pelvic floor disease characterized by abnormal(uncoordinated)contractions of the external anal sphincter and puborectalis muscle during defecation,resulting in rectal emptation and obstructive constipation.The clinical manifestations of SPFS are mainly characterized by difficult defecation,often accompanied by a sense of anal blockage and drooping.Manual defecation is usually needed during defecation.From physical examination,it is commonly observed that the patient's anal muscle tension is high,and it is difficult or even impossible to enter with his fingers.AIM To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome.METHODS Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome.All patients underwent pelvic floor surface electromyography assessment,anorectal dynamics examination,botulinum toxin type A injection 100 U intramuscular injection,and two cycles of biofeedback therapy.RESULTS After the botulinum toxin A injection combined with two cycles of biofeedback therapy,the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery(P<0.05).Moreover,the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery(P<0.05).CONCLUSION Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome.Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively.However,randomized controlled trials are needed.

Botulinum toxin type A for treating chronic low back pain:A double blinded randomized control study

BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contributor.The administration of Botulinum toxin type A(BoNT-A)has been found to alleviate back pain by relaxing these stiff muscles.While BoNT-A is approved for use in numerous conditions,a limited number of randomized clinical trials(RCTs)validate its efficacy specifically for treating LBP.AIM To study the safety and the efficacy of BoNT-A in minimizing pain and improving functional outcomes in patients of chronic LBP(CLBP).METHODS In this RCT,adults aged 18-60 years with mechanical LBP persisting for at least six months were enrolled.Participants were allocated to either the Drug group,receiving 200 Ipsen Units(2 mL)of BoNT-A,or the Control group,which received a 2 mL placebo.Over a 2-month follow-up period,both groups were assessed using the Visual Analog Scale(VAS)for pain intensity and the Oswestry Disability Index(ODI)for disability at the start and conclusion of the study.A decrease in pain by 50%was deemed clinically significant.RESULTS The study followed 40 patients for two months,with 20 in each group.A clinically significant reduction in pain was observed in 36 participants.There was a statistically significant decrease in both VAS and ODI scores in the groups at the end of two months.Nonetheless,when comparing the mean score changes,only the reduction in ODI scores(15 in the placebo group vs 16.5 in the drug group,clinically insignificant)was statistically significant(P=0.012),whereas the change in mean VAS scores was not significant(P=0.45).CONCLUSION The study concludes that BoNT-A does not offer a short-term advantage over placebo in reducing pain or improving LBP scores in CLBP patients.

Severe Botulism after Intragastric Botulinum Toxin-A Injection: A Case Series

Intragastric botulismus toxin-A (BoNT-A) is one of the new approaches in the treatment of obesity. We aimed to contribute to the literature by presenting the clinical features, laboratory findings and treatment responses of iatrogenic botulism cases due to intragastric BoNT-A administered in our clinic. All detailed medical information was obtained by accessing the medical records of the patients who were hospitalized and followed up and treated between September 2022 and December 2022, and the diagnosis of A.05.1 Botulism was entered according to ICD-10, and whose clinical findings were compatible with botulism disease and who underwent intragastric BoNT-A application beforehand. These records were obtained by examining this information. 10 patients who developed botulism after intragastric BoNT-A application between 01/09/2022 and 28/02/2023 were followed up in our clinic. All of the patients were women. The mean age was 35. The mean hospital stay was 9 days. Only 1 of our cases required intensive care. Good response to treatment was accepted as a complete or near-complete improvement in the clinical findings of the patients and all of them had a good response to treatment. Intragastric BoNT-A administration is a procedure that requires careful indication with a profit/loss calculation considering the potential side effects. In addition, attention should be paid to dilution rates and dose amounts.

Identification of Monitoring Organ in Bivalves for Early Warning of Paralytic Shellfish Toxins Accumulation

Bivalve farming plays a dominant role in mariculture in China.Paralytic shellfish toxins(PSTs)can be accumulated in bivalves and cause poisoning the consumers.A sensitive detection of PSTs can provide early warning to decrease poisoning events in bivalve consuming.PSTs are traditionally examined using the whole soft-tissues.However,PSTs accumulation varies dramatically in different tissues of bivalves.Some tough tissues/organs(such as mantle),which account for a large proportion of the total soft body,exhibit a lower accumulation of PSTs and make the toxin extraction time-and reagent-consuming,potentially decreasing the accuracy and sensitivity of PSTs monitoring in bivalves.To develop a sensitive and cost-effective approach for PSTs examination in massively farmed bivalves,we fed three commercially important bivalves,Yesso scallop Patinopecten yessoensis,Pacific oyster Crassostrea gigas,and blue mussel Mytilus edulis with PSTs-producing dinoflagellate Alexandrium catenella,and detected PSTs concentration in different tissues.For all three bivalve species,the digestive gland accumulated much more PSTs than other tissues,and the digestive gland’s toxicity was significantly correlated with the PSTs toxicity of the whole soft-tissues,with r^(2)=0.94,0.92,and 0.94 for Yesso scallop,Pacific oyster,and blue mussel,respectively.When the toxicity of the whole soft-tissues reached 80μgSTXeq(100g)^(−1),the regulatory limit for commercial shellfish,the digestive gland’s toxicity reached 571.48,498.90,and 859.20μgSTXeq(100g)^(−1) in Yesso scallop,Pacific oyster,and blue mussel,respectively.Our results indicate that digestive gland can be used for the sensitive and cost-effective monitoring of PSTs in bivalves.

Effect of Purified Paper Wasp Ropalidia marginata Venom Toxins on Different Biomolecules in Mice Serum

This study evaluated the effects of purified paper wasp Ropalidia marginata venoms on various biomolecules in the blood serum of albino mice. Changes in the concentration of some important macromolecules, i.e., proteins, free amino acids, uric acid, cholesterol, pyruvic acid, total lipids and glucose were noted down. These alterations were measured after intraperitoneal injection of 40% and 80% 24-hour LD50 purified Ropalidia marginata venom toxin. Serum total protein levels were found to decrease to 78% after 6 hrs, while serum free amino acid levels were significantly increased to 117% 6 hrs after venom injection compared to control. It was also found that serum uric acid levels increased to 138% after 8 hrs of venom injection compared to control. The increase in serum cholesterol i.e. (101% and 106%) and pyruvic acid increased significantly to a maximum value of 106% after 6 hrs of treatment at 40% LD50. Glycogen levels in the gastrocnemius muscle were found to decrease significantly (p-0.05) to 43% and 92% at LD50 after injection of purified Ropalidia marginata venom after 8 h and 80% at LD50 compared to control. Moreover, up to 71% and 81% were obtained at 10 hrs of treatment with the same dose. In the present study, the purified toxins significantly changed the levels of biomolecules in blood serum, indicating their wider effects on cellular physiology due to toxic effects and stress on the animal. These toxins can be good antigens and stimulate immune responses in experimental mice.

Prospective observational study to assess the validity of the functional disability score in patients with blepharospasm,hemifacial spasm and synkinesis treated with botulinum toxin injection

Background:Benign essential blepharospasm(BEB),aberrant facial nerve degeneration and hemifacial spasm(HFS)are all examples dystonia which,though not life-threatening,can have a significant impact on patient quality of life.The need for reliable self-rating surveys to monitor functional disability is fundamental.The Blepharospasm Disability Index(BSDI)is already a widely utilised and validated selfrating score for blepharospasm whilst the functional disability score(FDS)requires further validation.The principle aim of this study is to repeat validation of the FDS against the BSDI,which has been validated by several groups since its original description but only in patients with BEB.Methods:A randomised blinded prospective cohort study was conducted at a single unit on 38 patients with BEB,aberrant facial nerve degeneration and HFS.Patients were blinded to complete the FDS followed by the BSDI or the BSDI followed by the FDS with a 30-minute interval.Results:Both the FDS and BSDI were found to be reliable with high internal consistency and test-retest reliability.Both scales were also found to be moderately correlated with the Jankovic disease severity score.Conclusions:This study is the first to use the FDS as a rating scale in patients with HFS and aberrant facial nerve degeneration.It is also the first study to formally validate the FDS as an acceptable rating scale for patients with dystonia and in particular it provides validation for its use in patients with HFS and aberrant facial nerve degeneration.

Systematic evaluation of the efficacy and safety of botulinum toxin type A in the treatment of spastic cerebral palsy

Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.

短裸甲藻毒素(Brevetoxin,BTX)研究进展

短裸甲藻毒素(Brevetoxin,BTX)是一类能够引起神经性中毒症状的有害赤潮藻毒素,在世界范围内的分布越来越广,对水产品的质量安全带来严重威胁。本文就该毒素的化学组分与结构、生物转化、致毒机理、分析方法等国内外最新研究进展和政策变化进行系统的论述,并提出我国的应对措施,为我国的赤潮监控和贝类安全监测提供背景参考。

重组蜈蚣抗昆虫神经毒素rScolotoxin-Ssm2b对家蚕的经口急性毒性

以家蚕为模式昆虫,进行重组蜈蚣抗昆虫神经毒素r Scolotoxin-Ssm2b的经口急性毒性试验。采用叶片涂抹法分别给2龄起蚕添食质量浓度为0.625、1.250、2.500、5.000、10.000μg/m L的r Scolotoxin-Ssm2b,添食24 h测定的LC50值为4.84μg/m L。幼虫添食质量浓度为5.000μg/m L的r Scolotoxin-Ssm2b后2~5 min,出现口吐消化液、头胸部左右大幅摇摆、躯体扭曲、胸部膨大、头部突出、侧翻倒地等明显的中毒症状;添食后2 h,约80%的幼虫死亡。研究结果表明r Scolotoxin-Ssm2b对家蚕具有经口急性毒性,证明其有口服杀虫活性。

基于Bt毒素的杀虫蛋白理性设计与创新应用策略

Bt毒素是源于苏云金芽孢杆菌(Bacillusthuringiensis)的具有特殊杀虫功能的大分子蛋白,其制剂和转基因作物已广泛用于害虫防治,产生了巨大的经济和社会生态效益。围绕Bt毒素挖掘和提升其应用价值是持续研究的热点,特别是随着Bt毒素结构功能和作用机制日趋明晰,为其功能修饰和创新应用创造了条件,相关研究蓬勃发展,成效显著。大量研究表明,采用定点突变、结构域替换或融合以及抗独特型抗体模拟等策略,是理性设计活性更高、稳定性更强、杀虫谱更广、非靶标生物安全性更高甚至是可用于害虫抗药性治理的有别于母体Bt毒素的突变体、结构杂合体乃至功能效应物抗体等新型杀虫蛋白的有效手段;此外,采用催化毒素活化、驱动毒素靶向受体结合、促进毒素表达以及同源或异源杀虫材料复配或共表达的协同促效等创新增效策略,也是助推Bt毒素应用价值的重要手段。本文总结了Bt毒素结构功能和作用机制,梳理了基于Bt毒素功能修饰的突变体、结构杂合体以及功能效应物抗体等新型杀虫蛋白理性设计和基于Bt毒素功能增效的创新应用策略等相关研究进展,并结合作者团队在模拟Bt毒素杀虫功能效应物抗体靶向设计研发方面的最新成果,探讨了基于Bt毒素的杀虫蛋白理性设计与创新应用策略未来发展动向及潜在可行捷径,为相关研究提供较为全面的最新有价值的文献资料和启发思路。

A型肉毒毒素防治额部外伤瘢痕的美学效果及对血清TGF-β_(1)、BMP-7水平的影响

目的:探讨A型肉毒毒素防治额部外伤瘢痕的美学效果及对血清TGF-β_(1)、BMP-7水平的影响。方法:选取2020年7月-2022年10月笔者医院收治的84例额部外伤患者为研究对象,按随机数字表法分为观察组和对照组,各42例。对照组采用清创美容缝合联合外用硅凝胶制剂防治瘢痕;观察组采用美容缝合拆线后伤口两侧注射A型肉毒毒素防治瘢痕。拆线后3个月,统计比较两组瘢痕临床防治有效率、瘢痕评分[温哥华瘢痕量表(Vancouver scar scale,VSS)]、瘢痕疼痛或瘙痒程度评分[视觉模拟评分法(Visual analogue scale,VAS)]、患者满意度、血清转化生长因子β_(1)(Transforming growth factor-β_(1),TGF-β_(1))和骨成型蛋白7(Recombinant bone morphogenetic protein 7,BMP-7)水平及不良反应。结果:观察组VSS评分、瘢痕疼痛或瘙痒程度VAS评分低于对照组(P<0.05);观察组瘢痕临床防治有效率为90.47%,高于对照组的69.04%(P<0.05);观察组患者满意度高于对照组(P<0.05);观察组TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05);两组均未发生严重不良反应。结论:额部软组织外伤患者美容缝合拆线后伤口两侧注射A型肉毒毒素可抑制瘢痕形成,有效提升瘢痕防治有效率及患者满意度,其临床效果可能与调控血清TGF-β_(1)和BMP-7水平有关,且安全性较高,具有一定的临床应用价值。

儿童肺炎支原体肺炎肺泡灌洗液CARDS TX、HMGB1、TLR2表达及临床意义

目的研究肺炎支原体肺炎(MPP)患儿肺泡灌洗液中社区获得性呼吸窘迫综合征毒素(CARDS TX)、高迁移率族蛋白1(HMGB1)、Toll样受体2(TLR2)表达,探讨其在MPP发病中的临床意义。方法回顾性分析55例MPP病例组及20例对照组临床资料,同时检测两组支气管肺泡灌洗液(BALF)中CARDS TX、HMGB1、TLR2、TLR4、晚期糖基化终末产物受体(RAGE)及髓样分化因子88(MyD88)表达,体外检测不同浓度CARDS TX刺激下HMGB1、TLR2的表达并进行比较。结果与对照组相比,MPP组LYM绝对值计数、PA、CD3^(+)、CD3^(+)CD4^(+)、CD3^(+)CD8^(+)、CD3-CD19^(+)、NK cell、CD19^(+)CD23^(+)明显下降,CRP、LDH、D-二聚体、IgA、IgG、IgM、CARDS TX、HMGB1、TLR2、MyD88均升高,差异有统计学意义(P<0.05或0.001)。CARDS TX刺激后HMGB1、TLR2的表达升高,且呈正相关,差异有统计学意义(P<0.001)。结论CARDS TX可能通过HMGB1-TLR2-MyD88途径参与肺炎支原体(MP)的致病。

Gene therapy for human colorectal carcinoma using human CEA promoter controlled bacterial ADP-ribosylating toxin genes:PEA and DTA gene transfer

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Botulinum toxin injection improved voluntary motor control in selected patients with post-stroke spasticity

The effect of botulinum toxin type A injection on voluntary grip control was examined in a 53-year-old female, who sustained a hemorrhagic right middle cerebral artery stroke 3 years previously, which resulted in finger flexor spasticity and residual weak finger/wrist extension. The patient received 50 units of botulinum toxin type A injection each to the motor points （2 sites/muscle） of the left flexor digitorum superficialis and flexor digitorum profundus, respectively. Botulinum toxin injection led to weakness and tone reduction in the spastic finger flexors, but improved grip release time in grip initiation/release reaction time tasks. Improved release time was accompanied by shortened extensor electromyography activity, and improved release time likely correlated with blocked co-contraction of finger flexors during voluntary finger extension. This case report demonstrated that botulinum toxin injection improved voluntary motor control of the hand in a chronic stroke patient with residual finger extension.

Toxicity assessment and screening of tetrodotoxin in the oblong blowfish(Takifugu oblongus)from the Tamil Nadu Coast of Bay of Bengal,India

Objective:To assess the toxicity of the pufferfish Takifugu oblongus,from Chennai coast,Tamil Nadu,India and to detect the presence of Tetrodotoxin(TTX).Methods:The toxicity was evaluated by mouse bioassay using Swiss Albino mice which were expressed in mouse units(MU).Gross anatomical features were observed which is followed by histopathology of the dead mice tissues to establish the toxicity.Instrumental analysis for the presence of tetrodotoxin was also performed through GC-MS and HPLC.Results:The toxicity of ovary was the maximum with 163 MU/g and lowest toxicity was observed in skin with 75.88 MU/g.Histopathological analyses of the dead mice showed various cellular degenerations and inflammations.The amount of Tetrodotoxin detected through GC-MS and HPLC was more reliable and sensitive than the customary mouse bioassay as instrumental analyses were able to detect even nanograms of the toxin.Conclusions:The present study evidently proved that Takifugu oblongus is highly toxic and consumption of the same can pose serious threat for health and possible lethality to humans.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.