Histopathological and radiological investigations of the influence of botulinum toxin on the submandibular gland of the rat

The aim of the study was to correlate the sonographic features of Botox A injection in rat submandibular gland with the histopathological changes. Fifteen Wistar albino rats were randomly assigned to 2 groups. Group 1 (control group) consisted of 5 animals not given any substance. Group 2 was divided as “a” and “b” each consisting of 5 animals. A median cervical incision has been performed to the rats in group 2 and 2.5 U Botulinum toxin A reconstituted 0.1 ml physiologic saline was injected into the right gland. Sonograms were obtained before the application, at the first day of the Botox A application, in addition to group 2a on the 14th day, and on 28th day to group 2b. Gland size was lower in group 2a and 2b comparing to control group. The gland size of group 2b was lower than group 2a. There was no change in vascularization. There was no other histopathological change except lymphocytic infiltration in group 2. It was observed that Botox A injection does not have a direct effect on the cells in submandibular gland but it causes a homogenic shrinking in gland size without atrophy.     

Immunohistochemical and morphometric investigations of the influence of botulinum toxin on the submandibular gland of the rat

Immunohistochemical methods were used to study the effects of botulinum toxin A on the concentration of acetylcholinesterase in the submandibular gland of the rat. The toxin was injected into the glands of healthy adult female Wistar rats and immunohistochemistry performed on the excised organs. Morphometric measurements were also carried out to study changes of cell morphology after local applications of botulinum toxin A. Compared with untreated glands or glands injected with saline there was a decrease of acetylcholinesterase in the glands treated with botulinum toxin. As the cholinergic pathway of the autonomic nervous system plays an important role in eliciting secretion from the salivary glands, inhibition of secretion by local application of botulinum toxin could be considered a therapeutic option for the treatment of various diseases affecting salivary gland function. Received: 7 May 1998 / Accepted: 20 August 1998     

Tolerance of salivary gland botulinum toxin A injection under local anesthesia for the treatment of sialorrhea in children: An observational study

ObjectivesThe main objective of this study was to assess tolerance of botulinum toxin A injection into the salivary glands under local anesthesia in a pediatric population. Secondary endpoints comprised efficacy and side-effects.Material and methodsA retrospective observational study included children treated between January 2013 and March 2020 for sialorrhea and/or pharyngeal salivary congestion. Children were identified from the botulinum toxin A injection database. The study included 162 injection sessions in 55 children. Injections were performed under local anesthesia with nitrous oxide, after clinical location of the site. Epidemiological and clinical data, injection tolerance on the FLACC scale, treatment response and complications were recorded.ResultsFor submandibular gland injections, pain was absent in 81 cases, mild in 64, moderate in 4 and intense in 1. In parotid gland injections, pain was absent in 45 cases, mild in 89, moderate in 17 and intense in 1. Injection tolerance was significantly poorer (P < 0.005) in parotid than submandibular glands. Seventy-seven percent of the injections had a positive effect on sialorrhea. Fifteen patients presented transient adverse events: mainly dysphagia and paradoxical increase in sialorrhea.ConclusionSalivary gland botulinum toxin A injections in under local anesthesia were well-tolerated, safe and effective for children with sialorrhea and/or pharyngeal salivary congestion.     

The effect of botulinum toxin type a injection on compound muscle action potential in an in vivo rat model

Serial measurements were performed on the compound muscle action potential (CMAP) amplitude and the force generated by the rat lower hind limb flexors to investigate the time course of intramuscular injections of botulinum toxin type A (BOTOX®). Thirty animals were used in this in vivo rat model. CMAP amplitude and muscle force were measured at predetermined intervals for 28 weeks. Compound muscle action potential amplitude and force declined markedly the first 5 to 7 days after injection of BOTOX but recovered in a near linear manner. The response magnitude and recovery rate were dose-dependent. Recovery of CMAP amplitude preceded recovery of muscle force. No clear evidence of a systemic effect on the untreated leg or a concentration effect was found. CMAP amplitude may be useful in determining optimal timing of repeat injections in treating neuromuscular disorders.     

The effect of intranasal injection of botulinum toxin A on the symptoms of vasomotor rhinitis

PURPOSE: Vasomotor rhinitis (VMR) is a common disease that is unrelated to allergy, infection, structural abnormalities, and systemic diseases. Patients with VMR usually complain of nasal obstruction accompanied by profuse watery nasal discharge. The exact pathophysiologic mechanisms of VMR are not known. Some studies suggested that it results from an autonomic nervous system dysfunction. No effective long-term treatment modalities exist for the VMR. MATERIALS AND METHODS: Thirty patients with VMR were randomly and equally divided into 2 groups. The mean age was 38.46 years (range, 18-59 years; 1 men, 14 women) for group 1 and 41.60 (range, 29-62 years; 4 men, 11 women) for group 2. Five patients with VMR were accepted as a control group. Fifteen patients were injected 10 U of botulinum toxin A (BTX-A) (group 1) and patients in group 2 were injected 20 U to inferior and middle turbinates. Control patients were injected with saline solution into the inferior and middle turbinates. RESULTS: Total symptom scores generally decreased after the first week and increased after the eighth week. The symptoms of patients (nasal obstruction, sneezing, nasal discharge, and nasal itching) were scored from 1 to 5, with 1 as less severe and 5 as most severe. The statistical significance of the results was analyzed using Kruskal-Wallis and Mann-Whitney U test. When total symptom scores of group 1 (10 U BTX-A) were compared with the control group, there was a statistically significant difference regarding symptoms scores at all control weeks. There was also a statistically significant difference for total symptom scores between group 2 and control group, except for the first control week. CONCLUSION: Intranasal injection of BTX-A is a highly effective, safe, and simple symptomatic treatment modality with a long-lasting effect for patients with VMR. Botulinum toxin A may be a good alternative especially for the treatment of resistant VMR cases.     

A型肉毒毒素对大鼠下颌下腺作用的形态学及免疫组织化学研究

目的 :研究大鼠下颌下腺局部注射A型肉毒毒素 (BTX A)后不同时间形态学改变及对P物质 (SP)表达的影响。方法 :实验用 18只雌性Wistar大鼠 ,采用右侧下颌下腺注射BTX A模型 ,分别于用药后 6d、10d、30d处死动物 ,用组织形态学及免疫组织化学染色方法 ,观察BTX A作用不同时间下颌下腺组织形态学改变以及对SP表达的影响。左侧注射生理盐水作为对照组。结果 :大鼠注射BTX A不同时间下颌下腺中腺泡及腺管细胞形态发生改变。注射BTX A 6d后 ,腺泡细胞出现萎缩 ,以 10d组最明显 ,可见大量腺泡细胞萎缩 ,30d组萎缩的腺泡细胞量减少。各时间组萎缩的腺泡周围未见炎症细胞浸润及坏死发生。免疫组织化学结果显示 ,6d组BTX A注射侧腺泡周围SP免疫反应阳性纤维减少 ,与对照侧相比差异有统计学意义 (t =- 3.4 92 ,P <0 .0 5 )。 10d组BTX A注射侧腺泡周围SP免疫反应阳性纤维明显减少 ,与对照侧相比差异有统计学意义 (t=- 9.70 7,P <0 .0 1)。 30d组BTX A注射侧与对照侧SP免疫反应阳性纤维染色密度基本相同 (t =- 1.185 ,P>0 .0 5 )。结论 :大鼠下颌下腺注射BTX A可以导致腺泡及腺管细胞暂时性萎缩 ,SP表达暂时性减少 ,说明其可能通过这两方面共同作用而达到治疗多涎症的目的。     

The value of local botulinum toxin A injection in the treatment of the pain of aphthous ulcer

To determine the effectiveness of botulinum toxin type A to reduce pain of recurrent aphthous ulcer, a single blinded placebo controlled trial of botulinum toxin A injection was performed. A total of 70 patients were enrolled and randomly received a botulinum toxin type A 1 unit or placebo. The patients were asked to note the level of pain on the visual analogue scale for 6 days. They also had to record any eventual side effects or recurrence for 6 months. More patients quickly recovered following Botulinum toxin type A injection than placebo; they would feel almost no pain after about 3 days. Botulinum toxin type A exhibits quick pain treatment effect following injection on aphthous ulcer. The author also believes that it can prevent recurrence for at least 6 months after injection.     

Ultrasound-guided botulinum toxin A injection: an alternative treatment for dribbling

Dribbling (sialorrhoea) affects about 10 per cent of patients with chronic neurological disease. The variety of treatments currently available is unsatisfactory. This study was a clinical trial of the efficacy of ultrasound-guided, intraglandular injection of botulinum toxin A for dribbling, performed within the otorhinolaryngology department of the National University of Malaysia. Both pairs of parotid and submandibular glands received 25 U each of botulinum toxin A. Twenty patients were enrolled in the study. The median age was 15 years. All 20 patients (or their carers) reported a distinct improvement in symptoms after injection. Using the Wilcoxon signed rank test, there were significant reductions in dribbling rating score, dribbling frequency score, dribbling severity score, dribbling visual analogue score and towel changes score, comparing pre- and post-injection states (p<0.001). There were no complications or adverse effects during or after the injection procedure. Intraglandular, major salivary gland injection of botulinum toxin A is an effective treatment to reduce dribbling. Ultrasound guidance enhances the accuracy of this procedure and minimises the risk of complication.     

重复局部注射A型肉毒毒素治疗眼睑及面肌痉挛的疗效观察

目的:观察重复局部注射A型肉毒毒素(BTXA)治疗眼睑及面肌痉挛的长期疗效。方法:对80例眼睑、面肌痉挛的患者(眼睑痉挛75侧,面肌痉挛65侧),连续重复局部注射BTXA 4~20次,共886次,面肌痉挛每次剂量为22.5~32.5 U,眼睑痉挛为12.5~15.0 U。随访2~8年,观察其长期疗效。结果:起效时间多于治疗后2~3 d。眼睑及面肌痉挛治疗后部分缓解、明显缓解、完全缓解分别为0、67.7%、32.7%及1.4%、72.3%、26.3%,总有效率100%。随注射次数增加,药物剂量未增加,药效持续时间分别为(19.9±4.5)周及(20.7±4.2)周(P>0.05)。局部不良反应轻微、短暂。结论:重复局部注射BTXA治疗面肌及眼睑痉挛,在不需增加剂量的情况下,可长期维持其疗效和作用持续时间,而且是一种安全、有效和简便的治疗方法。     

Histopathological changes in parotid gland following submandibular gland failure: an experimental animal study

IntroductionSubmandibular glands are exposed to many effects due to diseases and therapeutic interventions. A study evaluating the effect of submandibular gland dysfunction on the parotid gland has not been presented in the literature.ObjectiveThe aim of this study was to evaluate the histopathological changes in the parotid gland following submandibular gland failure.MethodsThree groups of seven randomly selected female New Zealand rabbits weighing 2500–3000 g were studied. Unilateral and bilateral submandibular glands were removed in Groups 1 and 2, respectively. No procedure was performed in Group III, the control group. The parotid glands were removed 30 days later. Histological parameters were evaluated and graded between 0 (none) and 3 (severe). Differences between groups were compared using the Mann–Whitney U test.ResultsMean mucus accumulation in acinar cells was 2.57 ± 0.53 and 1.71 ± 0.75 in Groups 1 and 2, respectively (p < 0.05). This value was 0.57 ± 0.53 in Group 3, which was significantly lower than in Groups 1 and 2 (p < 0.05). Mean dilatation of the intercalated ducts’ lumen was 1.28 ± 0.48 and 1.57 ± 0.53 in Groups 1 and 2, respectively (p > 0.05). This value was 0.28 ± 0.48 in Group 3, which was significantly lower than in Groups 1 and 2 (p < 0.05). Mean mucus accumulation in the intercalated ducts’ lumen was 2.00 ± 0.81 and 1.00 ± 0.57 in Groups 2 and 3, respectively (p < 0.05).ConclusionThe findings of this study indicate that only 1 month after submandibular gland failure, the parotid glands exhibit significant changes.     

Oncocytic carcinoma in the submandibular gland: report of a case based on anti-mitochondrial immunohistochemical observations

Oncocytic carcinoma arising in the submandibular gland is a very rare tumor that has only previously been reported in nine cases. This paper describes an additional case of oncocytic carcinoma in the right submandibular gland. The patient was a 55-year-old Japanese male who was presented with a 3 cm right submandibular mass. Both radical resection of the tumor and right supraomohyoid neck dissection were performed. Histologically, the tumor cells exhibited an abundant eosinophilic cytoplasm, which appeared to be finely granular, and invaded the surrounding tissues. In addition, perineural invasion was also observed. Electron microscopy demonstrated the presence of an abundance mitochondria in the cytoplasm of the tumor cells. However, since the fine structure of cytoplasm was destroyed by fixation and embedding of the tissue for the light microscopy, the cytoplasm of the tumor could not be observed clearly. Immunohistochemically, anti-mitochondrial antibody positivity was evident in the cytoplasm of the tumor cells. Consequently, we diagnosed the mass as oncocytic carcinoma. Usually, electron microscopy is necessary to diagnose oncocytic lesions, but the paraffin-embedded tissue was not suitable for electron microscopy. Immunohistochemistry using an anti-mitochondrial antibody was found to be useful and helpful for the diagnosis of oncocytic lesions.     

The effects of botulinum toxin on hemifacial spasm: an electrophysiologic investigation

Forty-one patients with unilateral or bilateral facial spasm were studied by electrophysiologic examination. All patients received local treatment with botulinum toxin. In the patients and controls, the measurements of the blink reflex revealed changes that (1) may indicate a central origin of the spasm in some cases, and (2) make it likely that the trigeminal nerve influences the facial nucleus and is thus involved in the regulation of the spasm.     

Carcinosarcoma of the submandibular gland: an autopsy case

Malignant mixed tumors of salivary glands are classified as three types: carcinoma arising in a pleomorphic adenoma, the most common; benign metastasizing pleomorphic adenoma; and carcinosarcoma (true malignant mixed tumor), which is very rare [Ann. Otol. Rhinol. Laryngol. (1982) 91 342]. In carcinoma, both epithelial and soft tissue elements are malignant. In the context of previous reports, we discuss a case of carcinosarcoma of the submandibular gland including the results of postmortem examination.     

A型肉毒杆菌毒素对豚鼠鼻黏膜腺细胞凋亡的影响

目的　探讨A型肉毒杆菌毒素 (botulinumtoxintypeA ,BTA)对豚鼠鼻腔黏膜腺细胞凋亡的影响。方法　 1 8只雄性豚鼠随机分为BTA组和对照组。BTA组左侧鼻腔以浸有 1 0U (0 .2ml)BTA的Merocel作用 1h ,对照组以生理盐水代替BTA。分别于用药后第 1周、2周、4周全麻下切取豚鼠左侧下鼻甲黏膜 (每组 3只 ) ,4 %多聚甲醛固定后石蜡包埋。切片行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记 (TUNEL)和AB PAS染色。结果　BTA局部应用第 1、2周豚鼠鼻黏膜腺体及腺上皮中凋亡细胞显著增加 (P <0 .0 1 ) ,第 4周凋亡指数恢复正常。细胞凋亡主要发生在浆液腺。结论　BTA可诱导豚鼠鼻黏膜浆液腺细胞凋亡。     

Carcinoma ex pleomorphic adenoma of the salivary gland: an immunohistochemical study

The proliferative activity of the tumor cells and the expression of tumor-associated genes and sex steroid hormone receptors were investigated immunohistochemically in ten cases of carcinoma ex pleomorphic adenoma (Ca-ex-PA) of the salivary glands. These were analyzed in benign and malignant components separately, and then were compared with ten cases of the other malignant tumors [adenocarcinomas, not otherwise specified (ACN) and salivary duct carcinomas (SDC)] and ten cases of pleomorphic adenomas (PA). The results obtained in this study were as follows: (1) malignant component of Ca-ex-PA showed a higher incidence of PCNA and Ki67 than benign component of Ca-ex-PA. A significant difference between benign component of Ca-ex-PA and PA was not observed. (2) A significant difference in the incidence of p53, c-erbB-2, EGFR overexpression was observed only between malignant component of Ca-ex-PA and benign component of Ca-ex-PA. (3) The incidence of PCNA, Ki67, p53, c-erbB-2 overexpression in malignant component of Ca-ex-PA showed the highest data among the four groups. These results suggest that Ca-ex-PA acquired the particular biological behavior in contrast to the other salivary neoplasms in the long-standing process while PA undergoes malignant transformation.     

A histological study of the effects of different α-adrenergic and cholinergic agonists on the rat submandibular gland

Summary Rat submandibular glands were exposed to various sialagogues, including carbachol, clonidine, noradrenaline and cyclocytidine. The effects of these drugs were morphologically compared. Clonidine, which is an -2-agonist, caused no depletion of granules in the serous cells examined. Noradrenaline and cyclocytidine, which are -1-agonists, showed remarkable depletion of secretory granules in the serous cells. Carbachol caused visible and abundant salivation in the animals, but was found to produce only partial granular depletion of both serous and mucous cells. To induce experimentally a complete depletion of granular serous cells, cyclocytidine was found to be an excellent choice as a sialagogue with no side-effects on the cardiac and respiratory system.     

Treatment of an acute salivary fistula after parotid surgery: botulinum toxin type A injection as primary treatment

A salivary fistula is a relatively uncommon but troublesome complication after parotid surgery. Most cases are self-limiting and respond well to conservative therapy (compression dressings). However, this treatment may require weeks before its effect becomes evident. We present the first report of direct administration of botulinum toxin type A as an effective primary treatment for an acute salivary fistula after parotid surgery, in the absence of other, more conservative treatment. A 47-year-old man with a 7-day history of sore throat was found to have a parapharyngeal tumor originating from the deep lobe of the parotid gland. He underwent tumor removal via a trans-paroticocervical approach. However, on postoperative day 7, the patient was noted to have massive salivary discharge from the surgical incision during a meal. We administered a transcutaneous botulinum toxin type A injection without a pressure dressing. One day after the injection, the salivary discharge from the incision line disappeared completely and there was no evidence of recurrent sialorrhea in the 6 months following the procedure. This report suggests that the injection of botulinum toxin type A is a highly effective and relatively safe primary method of treatment for an acute postparotidectomy salivary fistula, and not merely an alternative to more conservative therapy.