琥珀酸索利那新片治疗膀胱过度活动症的效果分析

目的:观察琥珀酸索利那新片治疗膀胱过度活动症的临床效果。方法:回顾性分析我科收治的膀胱过度活动症患者共90例,所有患者均符合由中华医学会泌尿外科分会尿控学组制定的《膀胱过度活动症临床指导原则》。其中43例患者采用酒石酸托特罗定片治疗并设为对照组,47例患者采用琥珀酸索利那新片治疗并设为观察组,对比两组患者用药前后排尿症状和尿动力学参数变化、膀胱过度活动症症状评分表(OABSS评分)和前列腺症状评分(IPSS评分)变化以及不良反应发生率对比情况。结果:观察组患者用药后平均24 h尿急次数、平均24 h排尿次数均明显低于对照组,最大尿流率(Qmax)、初始尿意容量(FDV)、最大膀胱压容量(MCBC)均明显高于对照组,两组患者以上指标相比较,差异均有显著性(P0.05);两组患者用药后OABSS评分和IPSS评分均有所下降,但是两组相比,差异不具有显著性(P0.05);3两组患者用药后均有不同程度的不良反应,其中口干症状患者比例具有差异性(P0.05)。结论:琥珀酸索利那新片治疗膀胱过度活动症疗效确切,安全性高。     

Defining Efficacy in the Treatment of Overactive Bladder Syndrome

Patients seek treatment for overactive bladder syndrome (OAB) due to poor quality of life, and perceived improvement in quality of life (QOL) from medical therapy is multifactorial. Many feel that efficacy/success of medical therapy for OAB should not be linked to improvements in 1 or 2 endpoints, but instead should be linked to patient expectation and QOL improvement. Ideally, once patient-centered goals are defined, outcomes should be correlated with relief of symptom(s), patient satisfaction, and goal attainment expectations as a result of treatment.Key words: Overactive bladder syndrome, Patient-centered treatment, Medical therapy for OABOveractive bladder syndrome (OAB) as defined by the International Continence Society (ICS) consists of the presence of urinary urgency, with or without urge incontinence, usually with frequency and nocturia.¹ The prevalence rates in both men and women in the United States is estimated at approximately 17%.¹ The total cost of OAB for the year 2000 has been estimated at $12.6 billion.² This cost is made up of diagnostic, treatment, routine care, consequence, and indirect costs from loss of productivity. Due to prevalence and cost of this condition, there are significant resources being utilized to develop treatments that improve patient quality of life (QOL) and reduce the financial burden to society.OAB is a medical problem largely due to its negative impact on daily QOL. The subjective impact of urinary frequency and urgency (with/without urge incontinence) on psychosocial and physical well-being is an important aspect of caring for this group of patients. The severity and degree of bother associated with the symptoms of OAB can directly influence a person’s mobility, degree of social isolation, impairment in work-related activities, disruption of sleep, impairment of domestic and sexual life, and result in depression.³ Patients may also develop extreme coping strategies including self-imposed fluid restrictions, avoidance of social events and travel, and dependence on protective undergarments. OAB not only affects the lives of patients, but also the lives of their caretakers and their QOL. Thus, many patients and their caretakers seek out treatments that will help provide improvement in these aspects of their lives. Unfortunately, relatively few data are available on the effect of current treatments on patient QOL.Most clinical trials evaluating the efficacy of medications and other treatments related to OAB define success as efficacy based on improvements in primary and secondary clinical endpoints. Generally, these clinical endpoints include reduction in incontinence episodes, micturition frequency, urgency measures, and nocturia. The potential problem with this is that clinically significant changes in these parameters compared with placebo may not result in meaningful change in QOL for the patient or the caretaker and may result in discontinuation of medication. Failure to achieve meaningful changes in quality may be related to the fact that a particular symptom is not adequately changed or an adverse event impacts negatively on QOL. A strong argument for this is the poor rate of medication persistence seen in managed care patients with OAB that are significantly lower than reported discontinuation rates from clinical trials.^4–7 Persistence rates for OAB drugs range from 8% to 29% in studies with at least 1 year of follow-up.^4,5,7–9 When comparing extended-release (ER) formulations with immediate-release (IR) formulations, no significant difference was seen in persistence rates after multivariate analysis.⁶ In a study evaluating patient reasoning for OAB medication discontinuation, only one-third of patients cited a single reason for discontinuation, with most citing multiple reasons with a mean of 2.3 reasons.¹⁰ The more common reasons included: 46.2%, “didn’t work as expected”; 21.1%, “side effects”; 17.2%, cost; and 11.2%, “another medication/medical condition required me to stop.” Patient adherence with prescribed therapy is affected by perceived benefit, pill burden, complexity of dosing schedule, memory lapses, and adverse events.¹¹With patients seeking treatment for OAB due to poor QOL and perceived improvement in QOL from medical therapy being multifactorial, it is clear why many believe that efficacy/success of OAB medication probably should not be linked to improvements in 1 or 2 endpoints, but instead should be linked to patient expectation and QOL improvement. Ideally, once patient-centered goals such as the ability to perform certain tasks are defined, outcomes should be correlated with relief of symptom(s), patient satisfaction, and goal attainment expectations as a result of treatment. We need to establish more clear-cut evidence of how a myriad of factors affect treatment response.     

膀胱过度活动症的抗胆碱治疗及其不良反应

膀胱过度活动症(overactive bladder,OAB)是一种令人烦恼的疾病,它影响着人们生活的质量。病人常常表现为尿急,伴有或不伴有急迫性尿失禁,通常有尿频和夜尿的症状。虽然膀胱过度活动症的病因不是很明确,但是抗胆碱药物作为其治疗的基石,在减少膀胱储尿期的收缩,增加膀胱的容量,起着重要的作用。这类药物具有一定的安全性,副作用小,并且有着相似的疗效。尽管如此,当治疗膀胱过度活动时,抗胆碱药物种类的选择,其治疗的预期利弊平衡也应在考虑之中,尤其是合并有中枢神经系统或者心脑血管系统疾病的老年患者。本文通过查阅国内外新近相关的文献,从受体的选择,临床应用和不良反应等方面对7种抗胆碱药物进行综述。     

Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome

Objectives

To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB) refractory to antimuscarinic therapy.

Methods

All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox). The Global Response Assessment (GRA) score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.

Results

Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR) increased, and voiding efficiency (VE) decreased after treatment. Female gender (odds ratio = 3.75) was the only independent factor associated with the success. Female gender (coefficient = 0.74), low baseline overactive bladder symptoms score (coefficient = -0.12) and the presence of OAB-wet (coefficient = 0.79) were independent factors associated with therapeutic efficacy (i.e., GRA score). VE (odds ratio = 0.062) was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%).

Conclusions

The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01657409","term_id":"NCT01657409"}}NCT01657409     

Estimation of Potential Availability of Essential Oil in Some Brands of Herbal Teas and Herbal Dietary Supplements

Introduction

The aim of the study was to estimate potential availability of essential oil in some brands of herbal products.

Methods

A comparison was performed on the basis of the essential oil yield in the unprocessed raw materials such as leaves of peppermint and lemon balm and inflorescence of chamomile as well as herbal tea bags and in dietary supplements. The yield of essential oil was determined by distillation. Essential oil was analyzed by GC-FID and GC-MS.

Results

It was found that the average potential availability of essential oils in the products such as dietary supplements for the doses recommended by the producers is lower than in the corresponding tea infusions: for peppermint formulations approximately 6-fold lower, for the formulations with lemon balm about 4-fold lower, and for the chamomile preparations about 3-fold lower. It was found that essential oils extracted from herbal teas have a similar chemical profile with characteristic deviations in the amount of individual components, which arise from the origin of the raw material.

Discussion

In contrast to homogenous pharmaceutical herbal mixtures consistent with, the Pharmacopoeia requirements, herbal teas (available in grocery stores) and dietary supplements are often out of control in terms of the yield and composition of the essential oil, which is primarily responsible for the health benefits and aromatic qualities of these products. Analysis of the composition of the dietary supplements showed that they contain on average significantly lower amounts of plant material compared to the herbal teas.     

Availability of Essential Elements in Nutrient Supplements Used as Antidiabetic Herbal Formulations

Five brands of antidiabetic herbal formulations as tablets, Diabetex, Divya Madhu Nashini, Jambrushila, Diabeticin, and Madhumeh Nashini, from different pharmacies were analyzed for six minor (Na, K, Ca, Cl, Mg, and P) and 20 trace (As, Ba, Br, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mn, Rb, Sb, Sc, Se, Sm, Th, V, and Zn) elements by thermal neutron irradiation followed by high-resolution gamma ray spectrometry. Further Ni, Cd, and Pb were determined by atomic absorption spectrophotometry. Most elements vary in a narrow range by a factor of 2–4 while a few others vary in a wide range, e.g., Na (0.05–0.67 mg/g), Mn (26.7–250 μg/g), and V (0.26–2.50 μg/g). All the five brands contain K, Cl, Mg, P, and Ca as minor constituents along with mean trace amounts of Cr (2.11 ± 0.67 μg/g), Cu (15.7 ± 7.11 μg/g), Fe (459 ± 171 μg/g), Mn (143 ± 23 μg/g), Se (238 ± 112 ng/g), and V (0.99 ± 0.93 μg/g). Jambrushila is enriched in Na, Ca, Mg, Cl, Fe, Cu, Se, and Zn, essential nutrients responsible for curing diabetes. Dietary intake of Mn, Fe, and Cu are greater than 10% of the recommended dietary allowance, whereas that for Zn and Se is less than 2%. Mean contents of toxic elements (As, Cd, Hg, and Pb) were found below permissible limits except in Jambrushila. Cr and Zn were inversely correlated with r = −0.81, whereas Rb and Cs exhibit linear correlation (r = 0.93) in five brands. C, H, N analysis showed C ∼ 55%, H ∼ 12%, and N ∼ 2% with a total of ∼70% organic matter. However, thermal decomposition studies at 700°C suggest less than 5% nonvolatile metal oxides. Herbal formulations contain minor and trace elements in bioavailable forms that favorably influence glucose tolerance and possibly increase the body’s ability to ameliorate development of diabetes.     

Presence of Cleaved Synaptosomal-Associated Protein-25 and Decrease of Purinergic Receptors P2X3 in the Bladder Urothelium Influence Efficacy of Botulinum Toxin Treatment for Overactive Bladder Syndrome

Objectives

To evaluate whether botulinum toxin A (BoNT-A) injection and Lipotoxin (liposomes with 200 U of BoNT-A) instillation target different proteins, including P2X3, synaptic vesicle glycoprotein 2A, and SNAP-25, in the bladder mucosa, leading to different treatment outcomes.

Materials and Methods

This was a retrospective study performed in a tertiary teaching hospital. We evaluated the clinical results of 27 OAB patients treated with intravesical BoNT-A injection (n = 16) or Lipotoxin instillation (n = 11). Seven controls were treated with saline. Patients were injected with 100 U of BoNT-A or Lipotoxinin a single intravesical instillation. The patients enrolled in this study all had bladder biopsies performed at baseline and one month after BoNT-A therapy. Treatment outcome was measured by the decreases in urgency and frequency episodes at 1 month. The functional protein expressions in the urothelium were measured at baseline and after 1 month. The Wilcoxon signed-rank test and ordinal logistic regression were used to compare the treatment outcomes.

Results

Both BoNT-A injection and Lipotoxin instillation treatments effectively decreased the frequency of urgency episodes in OAB patients. Lipotoxin instillation did not increase post-void residual volume. BoNT-A injection effectively cleaved SNAP-25 (p < 0.01). Liposome encapsulated BoNT-A decreased urothelial P2X3 expression in the five responders (p = 0.04), while SNAP-25 was not significantly cleaved.

Conclusions

The results of this study provide a possible mechanism for the therapeutic effects of BoNT-A for the treatment of OAB via different treatment forms. BoNT-A and Lipotoxin treatments effectively decreased the frequency of urgency episodes in patients with OAB.     

Increased Serum Adipokines Implicate Chronic Inflammation in the Pathogenesis of Overactive Bladder Syndrome Refractory to Antimuscarinic Therapy

Objectives

Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy.

Methods

Thirty consecutive patients with OAB-dry (n = 16) or OAB-wet (n = 14) refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups.

Results

The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls.

Conclusions

Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were not relevant to medical diseases.     

Effects of Selenium and Zinc Status in Biological Samples of Hepatitis C Patient After Herbal and Pharmaceutical Supplements

The use of natural remedies and pharmacological mineral supplements for liver disease treatment has a long history. In present study, the levels of selenium (Se) and zinc (Zn) were determined in biological samples (serum and whole blood) of female hepatitis C patients (n?=?132), age ranged 30–45 years, before and after 30 days treatment with herbal/pharmaceutical supplements. For comparative study, 128 age-matched female subjects, residing in the same residential areas and have socioeconomic status, were selected as referents. The Se and Zn in supplements, blood, and sera were determined by atomic absorption spectrometry. It was observed that Zn and Se in blood and serum samples of viral hepatitis C (HCV) patients were reduced in the range of 28.6–39 % and 24–36 %, respectively, as compared to those of referents. After herbal/pharmaceutical supplementations, 20.6–25.0 and 9.15–13.2 % of Zn and 10.6–12.1 and 19.6–21.4 % of Se were enhanced in sera and blood samples of HCV patients, respectively. The resulted data indicated that the levels of Se and Zn in addition to some biochemical parameters were improved in HCV patients after herbal/pharmaceutical supplementation. The effects of both supplements were not significantly different (p?>?0.05).     

Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection on Elderly Patients with Chronic Central Nervous System Lesions and Overactive Bladder

Purpose

Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson’s disease (PD) and dementia.

Materials and Methods

Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups.

Results

A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions.

Conclusion

Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment.     

双氯芬酸钠栓和索利那新片治疗TURP术后OAB的临床疗效观察

目的:探讨双氯芬酸钠栓和索利那新治疗TURP术后OAB的临床疗效及预防性用药的必要性。方法:采取随机区组单盲的临床试验设计,将入选患者随机分为预防用药组和观察用药组。预防性用药组分别别使用双氯芬酸钠栓、索利那新片单药处理及两种药物联合处理,观察用药组在出现症状后按照预防性用药组的相同方法给药。结果:观察用药组中,双氯芬酸钠栓治疗的完全缓解率为50%,索利那新为81.8%,联合用药为90.5%,显著高于双氯芬酸钠栓(P0.05),各组不良反应的发生情况比较无显著性差异(P0.05)。预防用药组中,索利那新、双氯芬酸钠栓及联合用药分别可使TURP术后OAB的发生率降低45.0%、50.9%、53.8%.,三组之间比较无统计学差异(P0.05),且三组不良反应的发生情况比较无显著性差异(P0.05)。结论:双氯芬酸钠栓和索利那新治疗TURP术后OAB均安全有效,联合用药效果更佳,且预防性用药可以显著降低TURP术后OAB症状的发生率。     

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several techniques, including infusion of exogenous bacterial toxin (endotoxemia) or bacteria (bacteremia), as well as surgical perforation of the cecum by cecal ligation and puncture (CLP)^1-3. CLP allows bacteria spillage and fecal contamination of the peritoneal cavity, mimicking the human clinical disease of perforated appendicitis or diverticulitis. The severity of sepsis, as reflected by the eventual mortality rates, can be controlled surgically by varying the size of the needle used for cecal puncture². In animals, CLP induces similar, biphasic hemodynamic cardiovascular, metabolic, and immunological responses as observed during the clinical course of human sepsis³. Thus, the CLP model is considered as one of the most clinically relevant models for experimental sepsis^1-3.Various animal models have been used to elucidate the intricate mechanisms underlying the pathogenesis of experimental sepsis. The lethal consequence of sepsis is attributable partly to an excessive accumulation of early cytokines (such as TNF, IL-1 and IFN-γ)^4-6 and late proinflammatory mediators (e.g., HMGB1)⁷. Compared with early proinflammatory cytokines, late-acting mediators have a wider therapeutic window for clinical applications. For instance, delayed administration of HMGB1-neutralizing antibodies beginning 24 hours after CLP, still rescued mice from lethality^8,9, establishing HMGB1 as a late mediator of lethal sepsis. The discovery of HMGB1 as a late-acting mediator has initiated a new field of investigation for the development of sepsis therapies using Traditional Chinese Herbal Medicine. In this paper, we describe a procedure of CLP-induced sepsis, and its usage in screening herbal medicine for HMGB1-targeting therapies.     

中国岩黄芪属(豆科)植物资料增补

根据对标本的研究及文献资料的整理,证实了西伯利亚岩黄芪在中国的分布;山竹岩黄芪在新疆的分布新记录。另外,还报道了地中海岩黄芪在陕西的栽培记录。     

LIBS: A Quality Control Tool for Food Supplements

In the present paper the ability of calibration free laser induced breakdown spectroscopy (CF-LIBS) as a quality control tool to monitor the composition of different minerals present in food supplement samples belonging to Indian brands (brand-A and brand-B) has been demonstrated. LIBS spectra of these two food supplements (brand-A and brand-B) available in the form of tablet have been recorded. As reported by manufacturers of these two food supplements, LIBS spectra of brand-A contains the spectral signatures of minerals like Ca, Mg, C, P, Zn, Fe, Cu, and Cr whereas LIBS spectra of brand-B shows the presence of spectral lines like Ca, Mg and C. The spectral signatures of Na and K are also found in both brands whereas spectral signature of Ti is observed only in brand-B but these elements are not mentioned on the nutritional label of the brands. The quantitative analysis of mineral contents in food supplements has been done using CF-LIBS for brand A and brand B to verify the content of the minerals reported by the manufacturer of the food supplements. Our results show that Ca and Mg are the main matrix elements of these brands. The concentration of minor and trace elements estimated using CF-LIBS technique is found in agreement with the reported nutritional values of both the brands. The concentration of major elements Ca and Mg are also estimated from Atomic Absorption Spectroscopy which is in close agreement with CF-LIBS result.