A delayed treatment model for the evaluation of scopolamine for VX nerve agent intoxication.

Most research on medical countermeasures for nerve agent exposure assumes a military scenario, in which (autoinjector) treatment is envisaged to be available immediately. In a civilian setting however, treatment is delayed until arrival of first-aid responders. This may significantly affect treatment efficacy and the requirements for secondary intensive care. The aim of the current study was to develop a guinea pig model to evaluate the efficacy of delayed treatment following nerve agent exposure. We identified a trigger-to-treat based on a progressive stage of the toxidrome following VX exposure, which was associated with the subsiding of clonic movements. This paradigm resulted in treatment consistently being administered between 15 and 25 min post-exposure. Using the model, we investigated the potential for the anticholinergic scopolamine to act as a delayed treatment either as a standalone treatment, or as an adjunct to delayed treatment with Standard of Care (SOC), containing atropine, 2-PAM, and midazolam. The study provides a framework for a small animal model for evaluating the efficacy of treatment administered at a specific stage of the toxidrome, when immediate treatment is absent. As an adjunct, scopolamine treatment did not result in improved survival, but did show a beneficial effect on recovery, in terms of general posture. As a standalone treatment, scopolamine showed a significant, dose-responsive, beneficial effect on survival and recovery. These promising results warrant additional studies to investigate which observed physiological improvements are relevant for the recovery process and residual injury.

Deferiprone ameliorates memory impairment in Scopolamine-treated rats: The impact of its iron-chelating effect on ß-amyloid disposition.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive and memory problems. Scopolamine (SCOP) is a natural anticholinergic drug that was proven to cause memory impairment in rats. Chelating agents are potential neuroprotective and memory enhancing agents as they can trap iron that enters in pathological deposition of ß-amyloid (Aß) which is a hallmark in AD and memory disorders. This study investigated the potential neuroprotective and memory enhancing effects of the iron chelating drug, Deferiprone. Three doses (5, 10, and 20 mg/kg) were administered to rats treated with SCOP (1.14 mg/kg/day). Systemic administration of SCOP for seven days caused memory impairment which manifested as decreased time spent in platform quadrant in Morris water maze test, decreased retention latencies in passive avoidance test, and increased acetylcholinesterase (AChE) activity, Aß, and free iron deposition. It was observed that pretreatment with Deferiprone increased platform quadrant time in Morris water maze and increased retention latencies in the passive avoidance test. It also attenuated the increase in AChE activity and decreased Aß and iron deposition. Overall, Deferiprone (10 mg/kg) was determined as the most effective dose. Therefore, this study suggests neuroprotective and memory enhancing effects for Deferiprone in SCOP-treated rats which might be attributed to its iron chelating action and anti-oxidative effect.

Features of anticholinergic prescriptions and predictors of high use in the elderly: Population-based study.

PURPOSE: Older people are especially vulnerable to negative anticholinergic effects. Although anticholinergic drugs are commonly used among older people, drugs with potent antimuscarinic properties are considered as potentially inappropriate medications for older people. Here, we examined features of anticholinergic use and investigated predictors for the high use of strong anticholinergic agents (ACs) in the elderly. METHODS: A total of 388,629 Korean elderly aged ≥70 years were recruited from the 2012 National Health Insurance Service Elderly cohort database. The use of ACs in 2012 was quantitatively assessed by calculating standardized prescribed doses. Multivariate logistic regression was conducted to identify predictors of the high use of strong ACs (≥90 doses). RESULTS: Almost half of the subjects (47.2%) used more than 15 doses of strong ACs during 2012. 17.0% of the subjects had an annual cumulative use of strong ACs over 90 doses. Morbidities such as depression (odds ratio [OR], 95% confidence interval [CI] = 2.56, 2.48-2.63), Parkinson's disease (2.41, 2.26-2.56), genitourinary diseases (2.12, 2.07-2.16), polypharmacy (3.28, 3.21-3.36), and low income (1.29, 1.25-1.33) were strong predictors of their high use. Antihistamines (chlorpheniramine) and antidepressants (amitriptyline) greatly contributed to the total prescription of strong ACs. CONCLUSIONS: Despite the vulnerability of older people to the adverse reactions of strong ACs, their use seems to be at a high level in terms of cumulative usage among some elderly. More attention should be paid to older people with predictive factors of high use of strong ACs. Key points Despite the susceptibility of older people to negative anticholinergic effects, high use of strong anticholinergic agents was is quite frequent; 17.0% of the elderly had an annual cumulative use of these drugs ≥90 doses. Parkinson's disease, depression, genitourinary diseases, low income, and polypharmacy strongly predicted the high use of strong anticholinergic agents. A few strong anticholinergic agents, including antihistamines (chlorpheniramine) and antidepressants (amitriptyline), accounted for the majority of medications prescribed. Understanding the predictors of their high use by medical practitioners may result as more appropriate anticholinergic medications.

Intracerebroventricular microinjection of kaempferol on memory retention of passive avoidance learning in rats: involvement of cholinergic mechanism(s).

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.

Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide as a combination therapy for chronic obstructive pulmonary disease.

INTRODUCTION: The triple therapy term covers the combination of inhaled corticosteroid (ICS), long-acting ß-receptor agonist (LABA) and long-acting anticholinergic drug (LAMA) in one or in separate inhalers. The latest GOLD 2018 (Global Initiative for Chronic Obstructive Disease) guidelines recommend the triple therapy in the management of chronic obstructive pulmonary disease (COPD) in patients of group D who despite the combination of two drugs: LAMA/LABA or ICS/LABA continue to have persistent symptoms or suffer from further frequent exacerbations. Areas covered: The first triple fixed-dose combination of extrafine beclomethasone/formoterol/glycopyrronium in one pMDI type inhaler intended for the treatment of COPD has been registered in Europe in 2017. Pharmacokinetic and pharmacodynamic properties, clinical efficacy and safety of this triple combination are presented in the review. Expert commentary: A 20% reduction in the risk of moderate or severe exacerbation was found in patients receiving triple therapy compared to the ICS/LABA combination and LAMA monotherapy. Triple therapy reduces the number of exacerbations in comparison with double bronchodilatation (LABA/LAMA), thus representing an interesting therapeutic option in the management of COPD. The profile of side effects of triple therapy is typical for individual active agents included in the combination.

Interventional management of hyperhidrosis in secondary care: a systematic review.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. OBJECTIVES: To undertake a systematic review of the clinical effectiveness and safety of treatments available in secondary care for the management of primary hyperhidrosis. METHODS: Fifteen databases (including trial registers) were searched to July 2016 to identify studies of secondary-care treatments for primary hyperhidrosis. For each intervention randomized controlled trials (RCTs) were included where available; where RCT evidence was lacking, nonrandomized trials or large prospective case series were included. Outcomes of interest included disease severity, sweat rate, quality of life, patient satisfaction and adverse events. Trial quality was assessed using a modified version of the Cochrane Risk of Bias tool. Results were pooled in pairwise meta-analyses where appropriate, otherwise a narrative synthesis was presented. RESULTS: Fifty studies were included in the review: 32 RCTs, 17 nonrandomized trials and one case series. The studies varied in terms of population, intervention and methods of outcome assessment. Most studies were small, at high risk of bias and poorly reported. The interventions assessed were iontophoresis, botulinum toxin (BTX) injections, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland. CONCLUSIONS: The evidence for the effectiveness and safety of treatments for primary hyperhidrosis is limited overall, and few firm conclusions can be drawn. However, there is moderate-quality evidence to support the use of BTX for axillary hyperhidrosis. A trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.

The Role of Fixed-Dose Dual Bronchodilator Therapy in Treating COPD.

The incidence of chronic obstructive pulmonary disease (COPD) is rising in the United States, and the disease represents a significant source of morbidity and mortality. Primary care providers face many challenges in COPD diagnosis and treatment, as different clinical phenotypes require personalized treatment approaches. Patient adherence and inhaler technique also contribute to treatment outcomes. Around 48% of primary care providers are unaware of guidelines and recommendations for COPD diagnosis and treatment, which may lead to misdiagnosis or undertreatment of COPD symptoms. Inadequately treated COPD can impair patients' quality of life and ability to perform everyday activities. Long-acting bronchodilator therapy is the cornerstone treatment for patients with COPD; combinations of bronchodilators of different pharmacological classes have shown improved efficacy vs monotherapy. We review the rationale behind fixed-dose dual bronchodilator therapy, evidence for the 4 currently Food and Drug Administration-approved long-acting anticholinergic bronchodilators/long-acting ß2-agonists fixed combinations, patient suitability for the available inhaler devices, and practical guidance to optimize personalized care for patients with COPD.

Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

OBJECTIVES: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. MATERIALS AND METHODS: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. RESULTS: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC50) of ACh in the presence of atropine (10-6 M; P < 0.05) and ZAHE (1000 µg/ml; P < 0.01) was significantly higher than EC50of ACh alone. The EC50of 5-HT in the presence of ketanserin (10-5 M; P < 0.01) and ZAHE (1000 µg/ml; P < 0.05) was higher than EC50of 5-HT alone. Similarly, the EC50of histamine in the presence of pheniramine maleate (10-6 M; P < 0.01) and ZAHE (300 µg/ml; P < 0.01 and 1000 µg/ml; P < 0.05) was also significantly higher than EC50of histamine alone. CONCLUSION: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

A pharmacological evidence for the presence of antihistaminic and anticholinergic activities in Equisetum debile Roxb.

OBJECTIVE: The study was designed to evaluate possible antihistaminic and anticholinergic activities of Equisetum debile. MATERIALS AND METHODS: Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of E. debile were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system. RESULTS: A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 µM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 µM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed. CONCLUSION: Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of E. debile and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.

Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling.

Oleanolic acid is a naturally occurring triterpenoid and is widely present in food and medicinal plants. To examine the effect of oleanolic acid on memory deficits, we employed a cholinergic blockade-induced cognitive deficit mouse model. A single administration of oleanolic acid significantly increased the latency on the passive avoidance task and affected the alternation behavior on the Y-maze task and the exploration time on the novel object recognition task, indicating that oleanolic acid reverses the cognitive impairment induced by scopolamine. In accordance with previous reports, oleanolic acid enhanced extracellular-signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Interestingly, ameliorating effect of oleanolic acid on scopolamine-induced memory impairment was abolished by N2-(2-{[(2-oxoazepan-3-yl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide (ANA-12), a potent and specific inhibitor of tropomyosin receptor kinase B (TrkB), in the passive avoidance task. Similarly, oleanolic acid significantly evoked long-term potentiation in a dose-dependent manner, which was diminished by ANA-12 treatment as shown in the electrophysiology study. Together, these results imply that oleanolic acid ameliorates scopolamine-induced memory impairment by modulating the BDNF-ERK1/2-CREB pathway through TrkB activation in mice, suggesting that oleanolic acid would be a potential therapeutic agent for the treatment of cognitive deficits.

Evaluation of a pharmacist-led pilot service based on the anticholinergic risk scale.

OBJECTIVES: To determine primary care physician (PCP) acceptance rates of electronic medication therapy recommendations based on anticholinergic burden for high-risk elderly patients, and to evaluate potential associations between recommendation acceptance and patient-provider characteristics. SETTING: Two medical clinics within Dean Health System, an integrated health care organization comprising ambulatory surgery centers, medical clinics, community pharmacies, specialty pharmacies, a health plan, and a pharmacy benefits management company. PRACTICE INNOVATION: In this pilot service, the medical records of patients at least 60 years old who met the following criteria were evaluated bimonthly: 1) PCP visit within 2 weeks; (2) three or more inpatient hospitalizations or emergency department visits in the past year; and (3) ten or more active medications. Anticholinergic Risk Scale (ARS) scores of eligible patients were calculated, and medication therapy recommendations were sent electronically to PCPs for patients with an ARS score greater than 3. Post-visit recommendation outcomes were recorded. EVALUATION: Descriptive statistics were utilized to characterize patients, physicians, and recommendations. A generalized linear mixed effects model with physician specific random effects was employed to evaluate recommendation acceptance rates, and odds ratios were calculated to quantify associations between baseline patient/provider characteristics and the likelihood of recommendation acceptance. Changes in aggregate ARS scores were evaluated with the use of a paired t test. RESULTS: Fifty-nine patients were included in this pilot, with 89 medication therapy recommendations made to 21 PCPs. An overall recommendation acceptance rate of 50% (95% confidence interval [CI] 37%-63%) was observed. There were no significant associations identified between baseline patient/provider characteristics and medication recommendation acceptance. CONCLUSION: High recommendation acceptance rates were achieved with the combination of objective anticholinergic risk assessment and algorithm-driven medication therapy recommendations. The lack of identified associations between patient/provider characteristics and recommendation acceptance supports the future scalability of this novel service.

Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD.

INTRODUCTION: The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. METHODS: We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. RESULTS: During 2013, the medication collected was 7.4%-10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient's sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. CONCLUSION: The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence.

Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.

IMPORTANCE: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. EXPOSURES: Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. MAIN OUTCOMES AND MEASURES: Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTS: The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCE: Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Plasma cholesterol-lowering activity of gingerol- and shogaol-enriched extract is mediated by increasing sterol excretion.

The present study investigated the cholesterol-lowering activity of gingerol- and shogaol-enriched ginger extract (GSE). Thirty hamsters were divided into three groups and fed the control diet or one of the two experimental diets containing 0.5 and 1.0% GSE. Plasma total cholesterol, liver cholesterol, and aorta atherosclerotic plaque were dose-dependently decreased with increasing amounts of GSE added into diets. The fecal sterol analysis showed dietary GSE increased the excretion of both neutral and acidic sterols in a dose-dependent manner. GSE down-regulated the mRNA levels of intestinal Niemann-Pick C1-like 1 protein (NPC1L1), acyl CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5), whereas it up-regulated hepatic cholesterol-7α-hydroxylase (CYP7A1). It was concluded that beneficial modification of the lipoprotein profile by dietary GSE was mediated by enhancing excretion of fecal cholesterol and bile acids via up-regulation of hepatic CYP7A1 and down-regulation of mRNA of intestinal NPC1L1, ACAT2, and MTP.

Allergic rhinitis: meaningful and less meaningful combination treatments including reminiscences.

Allergic rhinitis (AR) results from a complex allergen-driven mucosal inflammation in the nasal cavity. Current guideline-based therapy for allergic rhinitis include oral and nasal antihistamines, topical and systemic glucocorticoids, decongestants, antimuscarinic agents, mast cell stabilizing drugs, leukotriene-receptor antagonists, and others. In spite of guideline recommendations, most patients are using multiple therapies in an attempt to achieve symptom control. Therefore, more effective therapies for the management of AR are clearly required. Recently, a novel fixed dose combination containing azelastine and fluticasone propionate has successfully been introduced. At present, it represents the only meaningful topical drug combination. Perhaps, it will be followed by others.

[Therapy-refractory overactive bladder: alternative treatment approaches]. / Die therapierefraktäre überaktive Blase : Alternative Therapieansätze.

The treatment of patients with overactive bladder (OAB) refractory to conventional treatment is gaining clinical significance. This article intends to review alternative therapy options for patients with OAB refractory to conventional treatment. A search of the PubMed database as well as the abstracts presented at the European Association of Urology and the American Urological Association annual meetings was conducted. Keywords used during this search included overactive bladder (OAB) refractory to conventional treatment, electromotive drug administration (EMDA), sacral neuromodulation, augmentation cystoplasty and cystectomy. Eighteen articles with an adequate number of patients were identified. All articles published before 2001 were not included in this analysis. Because of first-line treatment failure, 30% of the patients required alternative treatment. This included EMDA, botulinum toxin injections into the detrusor, sacral neuromodulation, augmentation cystoplasty or cystectomy. Based on this review it appears that a significant improvement in micturition parameters, continence and in quality of life was achieved. Overall EMDA, intradetrusor injections of botulinum toxin and sacral neuromodulation seem to be highly effective and safe. Augmentation cystoplasty or cystectomy remains the last choice of treatment in refractory cases.Overall EMDA, intradetrusor injections of botulinum toxin and sacral neuromodulation seem to be highly effective and safe. Augmentation cystoplasty or cystectomy remains to be the last choice of treatment in refractory cases.

Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation.

BACKGROUND: Autonomic denervation may suppress atrial fibrillation (AF) vulnerability. This study was designed to assess the short- to mid-term effects of botulinum toxin, a cholinergic neurotransmission blocker, on AF inducibility. METHODS AND RESULTS: A total of 23 mongrel dogs were studied. The sinus node and atrioventricular node epicardial fat pads were exposed through a right lateral thoracotomy. Botulinum toxin (Botox, 50 U per fat pad) or 0.9% normal saline (control) was injected into the center of each of the 2 fat pads. The electrophysiological effects were evaluated at 1, 2, and 3 weeks (7 to 8 animals at each time point) with and without cervical vagal stimulation. The vagal stimulation effects on the sinus and atrioventricular nodes were inhibited, and dispersion of atrial effective refractory period was lower at 1 week in the Botox group. Significant suppression of AF inducibility was observed at 1 week but disappeared at 2 and 3 weeks. These changes were not observed in the control group. CONCLUSIONS: Temporary suppression of vagally mediated AF, for at least 1 week, was achieved with botulinum toxin injection in this canine model. This effect might be associated with reduced dispersion of effective refractory period. A temporary autonomic block using botulinum toxin might be a novel therapeutic option for several clinical conditions such as post-cardiac surgery AF.

[Diagnosis and treatment of interstitial cystitis]. / Diagnostik und Therapie der interstitiellen Zystitis.

Interstitial Cystitis, first described in 1887 as an inflammatory disease of the bladder wall, is now regarded as a very common disease with an estimated number of unreported cases. Reasons for underdiagnosis is the widespread use of strict exclusion criteria. The disease can already be suspected by a careful medical history and physical examination in an early stage and then be treated with promising multimodal therapeutic approaches. In addition to a symptomatic oral therapy, local instillations with constituents of the protective glycosaminoglycan-layer are the most common therapeutic approach, because its defective integrity plays a key role in the pathogenesis of interstitial cystitis.

[Capsaicin and lidocaine usage in functional disorders of urinary bladder]. / Zastosowanie kapsaicyny i lidokainy w zaburzeniach czynnosciowych pecherza moczowego.

Most of the drugs in the treatment of functional disorders of the urinary bladder has a peripheral effect. Their work consists mainly in reducing detrusor contractility of the bladder, or effects on the afferent innervation. Anticholinergics are the first drugs of choice. An alternative pharmacological treatment is to eliminate the overactivity by acting on the bladder afferent innervation, while not inhibiting its contractility. One option is to modulate the pharmacological activity of sensory mechanisms governing the functioning of the bladder via the vanilloid receptor (TRPV1) and ancyrin (TRPA1). Intravesical treatment with capsaicin or lidocaine only partially reduces bladder sensation. Furthermore, clinical use of lidocaine in the treatment of overactive bladder (OAB) is reduced to intravesical supply before capsaicin instillation to reduce the symptoms associated with initial phase of C-fibres sensitization. This paper presents the current state of knowledge regarding the use of capsaicin and lidocaine in functional disorders of the urinary bladder, as well as discusses the impact of these substances on afferent C-fibres and the activity of the urinary bladder. Based on previous studies intravesical capsaicin and lidocaine therapy is one of the alternative treatment options in selected patients with functional disorders of the urinary bladder (in particular OAB) in addition to standard anticholinergics therapy or the newer generation of therapies using botulinum toxin.