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斩草除根范文1
今天,天气晴朗我们班经过校长允许,准备到草坪里去把那些野的根拔起来。前一天宋老师还专门通知我们带了一根筷子。
上午第四节,我们来到花园,学着老师的样子把野草的根拔了起来。先找到野草 ,然后筷子轻轻的把土撬松,一边撬一边就往上拉。 可由于我们是第一次学动作慢,一会不是把根拉断,就是撬不动土。有些野草的根实在太长了,只得请老师来帮忙,老师轻轻松松的就的就把那些很长的根一一拔了出来。有一次一根太长了的根我拔不起来,正准被备去找老师,那一边的同学又把老师叫了过去,我想先自己拔着吧。可是拔了好久都拔不起来,我有些气馁了,可又看见许多同学也拔不起来,可是他们还在拔,我又蹲下身子拔了起来,最后功夫不负有心人,我终于拔了起来。
通过这件事我明白了,做什么事都要有信心和恒心!
斩草除根范文2
[关键词]艾滋病;民间组织;发展现状;组织结构;趋势
[中图分类号]C30
[文献标识码]A [文章编号]1672-2426(2009)09-0063-03
一、调查工作情况
调查对象、类型、数目:本次调查样本总计为35个民间组织,以男同志组织居多,计17个,接近半数;感染者组织居次,8个;性工作者关爱组织3个;其他组织7个。
调查方法:由于研究对象的敏感性,不便于实行公开的集体性的问卷调查。主要通过实地考察、个人约谈,辅之以电话访谈等方法。对调查材料进行交互性验证和描述性分析。
二、调查的初步认识
1 防艾草根组织的发展现状。前期对低流行区防艾草根组织调查发现,至2007年8月,防艾草根组织已经发展至94家,相比2006年7月增加了58家。其特点如下:
其一,组织数量迅速增加,地区差异明显。近些年,我国低流行区防艾草根组织的总体数量迅速增加。在调查的七个省(自治区、直辖市)中。防艾草根组织数量均有不同程度的增多。其中黑龙江防艾草根组织数量增加最多,山2006年的8个增加到2007年的30个;宁夏和辽宁防艾草根组织数量增加最少,分别由2006年的2个和14个增加到2007年的3个和15个。
就发展水平而言,地区间也不平衡。有些地区建立组织较早,发展的较为成熟,如辽宁、黑龙江;有些地区则相对落后,即有的组织都是近两年才成立,尚处在初建阶段,如内蒙古、宁夏。组织类型发展也不平衡,相对而言,同志组织发展领先于其他组织。但总体上表现出良性的发展态势,在防治艾滋病的事业中发挥出重要作用。
其二,组织类型不断丰富,各类型组织所占比例变化不大。通过调查发现,经过一年的发展,防艾草根组织的类型不断丰富,出现了一些新型组织,例如流动人群组织和男性工作者(MB)组织等。各类型防艾草根组织的数量变化如下:同性恋(MSM)组织由2006年的24个增加到2007年的60个;感染者组织(PLWHA)由2006年的5个增加到2007年的14个;性工作者(sw)组织由2006年的1个增加到2007年的6个;流动人群组织由2006年的0个增加到2007年的7个:其他由2006年的6个增加到2007年的8个。
其三,组织活动能力增强,对项目依赖程度变大。通过观察发现,近几年在国内外相关项目的大力支持下,我国防艾草根组织在组织资源动员能力上不断增强,呈现出不同的组织发展程度。依据防艾草根组织的年资源动员能力不同,可以将防艾草根组织分为三个发展层级(如表1)。
此外,相关调查显示,防艾草根组织的收入大部分来自于境外机构、企业和个人捐赠和政府资助,通过收费等活动获得的收入极少;有时靠组织负责人的个人出资。可见,防艾草根组织自身的生存能力较弱,对外部资助的依赖性比较大。
综上,虽然近些年我国防艾草根组织在数量、能力方面均有不同程度的增强,但总体上还处于起步阶段。尤其是近一年来,新成立的草根组织数量增多(调查中新增组织数量占现有组织数量的61.7%),其发展时间短、程度低,且对项目的依赖性大。基于此种情况,大多数防艾草根组织还是运作型组织,即自己筹资,自己开展项目。甚至部分组织长期处于间断运作的状态。
2 防艾草根组织的共性特征。通过面上调查和实地访谈,我们确认,作为将防治艾滋病作为组织宗旨和主要活动内容的直接面对特殊人群的民间组织,防艾草根组织具有草根组织的共性特征:
其一,注册组织数量少,多数组织未注册。防艾草根组织注册方式多为工商注册,民政注册的很少,更多的组织尚未注册。
其一二,组织规模小,活动范围以本地为主。调查显示,防艾草根组织的核心成员数量在1-15人。受组织发展程度的制约,多数防艾草根组织的组织活动范围以组织所在市为主,少数组织扩展到组织所在省或相邻省。
其三,组织活动对项目的依赖性大,多数组织开展活动的资金来源以项目经费为主。
3 防艾草根组织的组织结构。针对不同目标人群的防艾草根组织按照发展程度可分为三类:即自助型组织、服务型组织和政策倡导型组织。不同发展程度的防艾革根组织在组织构建和人力资源构成上都柯不同程度的差异。
其一,雏形期的组结构。该类组织结构极其简单、不成熟,为多数组织能力小,社区基础薄弱的自助型组织所采用。组织成员一般由组织负责人和个别的志愿者构成,领导者向下直接面对志愿者,运行方式通常为组织负责人的决策制定和组织志愿者的具体执行。
其二,发展期的组织结构。与雏形期的组织结构相比,发展期的组织结构是其发展的方向,也是许多被调查的防艾草根组织现在使用的组织结构形式。在该类组织结构中,组织负责人改变了直接面对志愿者的状况,可以通过少数固定的核心成蹦执行自己的决策。志愿者在组织中的主要任务是辅助核心成员执行组织负责人决策,进行相关的活动。
其三,成熟期的组织结构。政策倡导型组织多采用成熟期的组织结构进行管理。对于政策倡导型组织,其经过了起步阶段和发展阶段后组织能力不断增强,也吸引了一定数量的专职人员加入组织,并参与组织的管理工作。从组织调查和相关人员访谈信息来看,该类组织的管理结构也是目前比较完善且受到较多认可的组织结构形式。在该类组织结构中,组织负责人不再直接面对具体的活动执行人员,而是在组织专职人员中选出一名综合能力较强的人作为协调员,由其具体负责向成员下达组织负责人决策并组织实施。同时,组织负责人也指派了专人负责组织信息和经费管理。
4 人员构成与利益相关者。从前述组织结构可见,防艾草根组织的人员构成主要有=三类:组织负责人、项目组核心成员和志愿者。
其一,组织负责人。组织负责人是防艾草根组织的灵魂,多为组织的发起者,其领导能力和综合素质对防艾草根组织项目管理具有决定性影响。
其二,项目组核心成员。项目组织核心成员指负责人之外在组织中承担一定管理职务的人员,包括专职和兼职管理人员,如协调员、信息管理员和经费管理员等。由于防艾草根组织不能利
用高薪来吸引人才,且工资的提供又有很大的弹性(收入往往以固定补助或具体活动补助的形式发放),所以组织中的专业人员和专职人员的比例也小大。
其三,志愿者。志愿者是防艾草根组织开展项目的重要支柱。所有组织均是志愿者的数量比组织自身成员数量多,志愿者在组织内部扮演的角色多是具体任务的执行者的角色,且流动性大。与组织(尤其是组织负责人)间发生矛盾的情况也时有发生,影响了防艾草根组织管理工作的正常进行。这也是很多防艾草根组织在志愿者管理方面的困扰所在。
防艾草根组织的利益相关者主要是:
其一,政府机构。政府机构与防艾草根组织的关系应该是补充与互助的关系。政府机构作为社会管理的主体,为防艾草根组织提供政策和资源,尤其是以疾病预防控制中心和医疗机构为代表的卫生部门为防艾草根组织提供可靠的、高治疗的技术支持;当然,防艾草根组织也会在一定程度上影响和加速政府的政策制定和态度转变过程。
其二,目标人群。目标人群是指在疾病检测、预防或控制中,为达到预期目标而对其进行检测、预防或干预的靶人群。在艾滋病防治中,目标人群主要包括HIV感染者和艾滋病病人、受HIV/AIDS影响的人群以及HIV/AIDS易感人群。
其三,资助方。资助方通常有国家、省市等各级政府、国际机构(如联合国艾滋病规划署、世界银行和不同国家的政府)、国际非政府组织(如乐施会、救助儿童会)、国内基金会和研究机构等。资助方与民间组织应当是平等合作的关系,资助方通过提供资金、技术等方式为防艾草根组织提供各种资源,防艾草根组织通过相应的项目活动实现资助方的组织意愿,但事实上双方并不平等,资助方往往更为强势。
其四,合作方。防艾草根组织的合作方为组织发展提供了多方面的支持,包括进行项目申请、实施、评估等工作。例如酒吧老板、教育研究机构等。合作方通过参与防艾草根组织管理活动实现自己的目标,例如间接提高经济效益、满足资源需求等。
其五,竞争伙伴,对于某一特定的防艾草根组织而言,其竞争伙伴通常指与该组织处于同一地区、服务人群相同或相近的其他组织。当面对相同的潜在资源时,防艾草根组织与竞争伙伴之间表现为竞争关系,一个组织对资源的占有必然意味着对其他组织可利用资源的剥夺;当面对政府、市场时,防艾草根组织与竞争伙伴之间表现为合作关系,彼此通过经验交流、信息共享等可以相互促进、共同发展,以实现提升服务人群的整体生存状况。
其六,组织成员和志愿者。
三、防艾草根组织的发展路径与模式
1 生成路径。从革根组织成立的机缘与生成路径看,可以大体概括出几种模式:一是社群人士自发组建或由其他组织分化而来,可称内生模式,如心连心,阳光家园,爱心天空网站等。二是社群外爱心人士或公益机构组建,可称外生模式,如向日葵工作组、爱心岛等。三是疾控(项目办)或卫生机构出于工作或项目考虑出面组建,可称疾控模式,如真爱家园,牧人敖包工作室。疾控模式亦属外生模式,但自己的特点明晰,与其他外生组织有很大区别,所以作为单独一种模式。
不同生成模式对后来的发展与活动开展有很大影响。内生模式,有较大的社群号召力,环境适应性,可持续发展能力强,适于开展干预工作,工作的渗透力和效果亦强,但相对封闭,社会认知度不高。疾控模式与疾控等资助机构亲近,关系和谐,得到专业技术支持和项目资金比较直接,活动条件和组织发展的资源在防艾专项领域和特定时间周期内较有保证,但组织目标集中。对疾控和项目的依附性和依赖性强,工作的自主性低,往往受制于疾控人员和项目方的干预控制。社群外模式与社会公益力量更近,开放性强透明度高,易于得到社会的理解认同,但在社群开展活动的深度有限,往往为配合疾控工作或社群组织的项目而开展活动。适于从事一般性的宣传工作和倡导活动,做社群与社会之间的沟通。
不论何种生成模式,这些组织在建立、发展过程中都得到疾控或其他卫生机构如医院、医学院等的支持帮助,专业卫生医务人员直接或间接发挥作用。在社群人士未及参与之时,甚至直接出面建立组织。这些组织与特定社群及服务对象建立了相应的工作关系,在一定范围内取得了社群和社会的理解、认同,具备进一步发展的基础。
2 地方特征。值得注意的是,在不同地区,组织发展模式呈现明显的差别,模式与地区有很强的关连性。
东北三省的草根组织发展模式,主要是“自下而上”的内生式。以同志草根组织为例,早期成立的组织是由社群中经常接触的一些活跃分子发起的,他们大多自我认同良好、性格开朗、交往能力强、富于同情心。成立组织的目的是为了保护这个社群成员的健康。基于对本群体的了解、理解和关怀,起初他们自筹资金搞防艾工作,逐渐地在防艾领域有了声望,常常配合疾控和红会完成一些工作。由于工作范围和组织规模的扩大,依靠组织成员自筹资金是不现实的,很难维持组织的继续运行。这就促使草根组织从其他方面寻找资金,如申请项目支持。
在内蒙古、甘宁地区,草根组织发展模式的特点是“自上而下”的疾控式。从组织的成立到组织的运行,大都在疾控的促进领导下进行的。具体体现在:
首先,该地区的防艾工作是随着有关项目的出现而开始的。据了解,2006年国家有关防艾项目覆盖到,促使当地疾控加大在防艾领域的关注与投入。如疾控、呼和浩特市疾控分别设立了专门的办公室,安排专人负责防艾项目。
其次,该地区的草根组织是在疾控的动员和支持下成立的。为了能利用项目资金开展防艾工作,疾控深入调查并挖掘潜在的草根组织,以及有意愿成立组织的特殊群体中的人员,鼓励和支持他们成立小组。如阳光工作组就是在疾控的动员和支持下成立的,主要从事MSM人群的防艾工作。至今已经运行两年多了,组织规模在不断扩大,艾滋病的干预范围在扩大,在防艾领域发挥的作用越来越明显了。
第三,该地区草根组织是在疾控主导下运行的。这一点在财务上体现的最为明显。在访谈中我们了解到,有些项目资金是由疾控托管的,草根组织执行防艾工作所需要的资金经常要自己先行垫付,之后拿票据去疾控报销,而且财务报销流程相当繁琐,常常阻碍工作的进行。就连外展所需要的资料与物品,也都由疾控全权办置。用小组人员的话说,就是“项目从开始到最后,我们都看不到钱。我们需要什么,就跟疾控申请,由它们代购代办。”其实,在项目的执行过程中,很多环节都是机动灵活的,小组应该根据具体情况做适当地调整。然而,如此硬性的资金管理制度,无疑造成了项目执行的效率低下,
不利于小组工作的顺利开展。
从上述的发展模式中,我们可以看到主观和客观两个方面的因素在共同起作用。首先是社群中的人员有成立组织服务于本社群的意识,这种主动性是组织发展壮大的关键因素之一。其次是客观条件促进。仅有艾防意识并不够,还须有资金支持。像GF5(即全球基金第五轮防艾项目)项目、疾控和国家的一些项目都为草根组织提供了有利条件。比如位于北部边疆,其经济发展相对落后,人们的思想意识也相对保守。这应该是内蒙古没有自发成立的草根组织的主要原因。由于GF5项目覆盖到,疾控才动员社群人员成立草根组织来申请并执行项目。可以说是项目推动了草根组织的产生,为了项目而成立组织。为项目而项目,为项目而组织,这样的主观认知显然不具有可持续性,但这又是内蒙古革根组织发展的必经阶段。草根组织将来发展如何,关键取决于观念的转变,就是要正确理解组织存在目的和意义。
另外,组织发展还有一种增值一分裂增长模式。如呼市同心工作组的负责人不到30岁,很善谈,思想前卫。他曾是阳光工作组的志愿者,后来因为做事意见不合,分道扬镳成立了自己的同心工作组。沈阳的爱之援助工作组与阳光工作组;鞍山的同志社区工作组与鞍山好兄弟工作组。它们的负责人原来都是同一个工作组的,后来因意见不合,各立门户。
这种分裂模式是否是防艾草根组织增值的主要模式呢?这有待于我们考察更多的草根组织来验证。
3 共性问题。不论何种模式,草根组织目前存在的较为普遍的共性问题是:
(1)这些组织在经费和办公场所等方面存在缺陷,一般没有专门的办公场所,有些要么是在负责人的家中或单位,要么即便租有专门的办公场所也是相当简陋。在经费上多没有固定的来源,资金缺乏,开展活动比较困难。目前大多组织生存与防艾活动已经形成对特定防艾项目的强依赖性,能够开展经常性工作的组织往往仰赖球五项目的经费支持,有的组织也有来自红十字会的项目支持。有人表示,如果没有了球五项目则很难保证它们还能很好地维持下去,可见组织的自我生存能力薄弱是一个严峻的问题。
(2)组织内部建设与管理不规范,如财务制度不健全,经费有限却管理粗放,不够透明,资金安全性缺乏保证,由此常常引起社群与志愿者的误解与议论,甚至纷争不断。
(3)组织志愿者不稳定。此点是目前各类草根组织的共性,不赘述。
(4)项目开展水平低,不规范。如监督不足,很多防艾草根组织在成功申请到项目后便进入放任阶段,很少对项目实施过程给予监督。又如评估工作只重形式不重内容,只重成功经验推广不重失败教训吸取。
斩草除根范文3
这个作文网,是我梦想的网站,因为我热爱作文,视我生命的一切,我以后也有当个作家这样的梦想,但是,现实让我看到了什么,肮脏!梦想的网站,真正的公平,没有抄袭,大家不管关系多好,绝不会因为人缘投票,而且可能有的人缘很好的人一堆都是他自己的账号!我看不惯这肮脏,我想改变它,尽管我知道网络无穷的大,但是,能改变一点就是要改变,所以,你们可以看出我是一个小孩子。
我很喜欢“我来写‘春联’”这个活动,不仅仅因为它的奖品很好,让我想得到,更因为这个可以开发我们无穷的创造力,想象力。真的也有人写的无穷的好。但是,我在看了后面的春联以后,发现有一个人抄袭,我就和她说:“你抄什么啊,你以为我们都是瞎子吗?”我是真的忍不住了,谁知,她竟说:“你有什么证据啊,怎么能这么说呢。”这是一个网友,叫许荔楠。我真的很诧异,你说你抄了就抄了吧,你为什么死活不承认呢?!
还有一件事情我不明白,为什么我的作文好像已经过了七天,还没有审核结束呢?不会是因为我的太好被震住了吧!呵呵,开个玩笑。虽然我喜欢作文,但是这件事情令我很生气,我只能用这种方式告诉站长。
斩草除根范文4
2、拼音:sǎo dàng。
3、引证释义:柳青《铜墙铁壁》第七章:“经过两昼夜的扫荡战,消灭了二十二军两个团。”
4、例句:飙车族破坏了社会秩序,警方决定斩草除根,全面扫荡。
5、近义词:涤荡。
斩草除根范文5
1、不可以。蟑螂不怕酒精,酒精很容易挥发掉,所以酒精对于蟑螂来说构不成威胁,生活中酒精也无法驱除并消灭蟑螂的。蟑螂是比较怕没有水源的地方、怕洋葱的刺激气味、怕黄瓜、怕芥末、怕老鼠、怕洗衣粉兑水的喷剂等。
2、可以用洗衣粉水进行拖地,或者直接撒洗衣粉在室内墙角。一般情况下蟑螂繁殖很快,所以如果想要消除蟑螂卵的话,必需要把卵鞘踩碎,或者用开水烫、用火烧,这样才能杀灭蟑螂卵的活性,斩草除根。拍死蟑螂后在地上用84消毒液清洗是不能消除蟑螂卵的,只可以给地面消毒。
(来源:文章屋网 )
斩草除根范文6
【关键词】 幽门螺旋杆菌; 胃滞留剂; 漂浮剂型; 草药; 黑柯子; 黄连素
Helicobacter pylori are very common pathogenic bacteria colonizing about half of all populations and associated with the development of serious gastroduodenal diseases like gastric lymphoma, peptic ulcers and acute chronic gastritis. Current drug regimes are not wholly effective. Other problems related with the current drug regimes are lack of patient compliance, side effects and bacterial resistance. Thus, drug delivery to the site of residence in the gastric mucosa may help in solving the problems associated with the current drug therapy. Gastric retentive delivery systems potentially allow increased penetration and thus increased drug concentration at the site of action. Floating drug delivery systems, expandable or swellable drug delivery systems and bioadhesive systems are the major areas of interest to formulate gastroretentive drug delivery system against H. pylori. Generally, problems with these formulations are lack of specificity and the dependence on mucus turnover, so they fail to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucusepithelial interface. Gastroretentive delivery strategies, specifically with regard to their application as a delivery system to target Helicobacter, are a very attractive field which can cure these troublesome infections.
H. pylori is a Gramnegative, microaerophilic, spiral and flagellated bacterium, with unipolarsheathed flagella that provides motility. Its spiral shape and high motility allows it to penetrate mucus, resist gastric emptying and remain in the host gastrointestinal (GI) tract. It is now firmly established that infection with this bacterium is the cause of chronic active gastritis. Its isolation radically changed the conceptualisation of several chronic gastrointestinal illnesses including gastritis and peptic ulcers, and elimination of the causative organism became the goal of therapies [1]. Estimates from the WHO in 1994 claimed that about half of the world’s population was infected with H. pylori and although most infections are silent, a portion of the infected population will subsequently present with associated disease including chronic gastritis, peptic and duodenal ulcers. About 550 000 new cases a year of gastric cancerabout 55% of the worldwide totalwere attributed to H. pylori, and it was predicted that by 2020 to enter the top ten of leading causes of death worldwide[2, 3]. H. pylori is a very perse specy and cancer risks may be increased with strains having virulenceassociated genes (cytotoxinassociated gene, CagA), host genetics and environmental factors. The incidence of infection is higher in developing countries with up to 80%90% of adults being infected whereas in developed countries prevalence ranges from 10%50%[4].
1 Mechanism of H. pylori infections
Infection with H. pylori occurs predominately in childhood mainly between the ages 1 to 5, via oral ingestion of the bacterium, and lasts until the end of life with intrafamilial transmission being the major route in developed countries. The possible routes of transmission are food and water. The major feature of H. pylori infection is progressive injury to the gastric mucosa and its function[5, 6]. The bacterium adheres to the gastric epithelial cells, producing a direct injurious effect that is then amplified by production and release of a vacuolating cytotoxin (VacA)[7, 8]. H. pylori produces a variety of enzymes and is characterised by a high urease activity. Urea is broken down into bicarbonate and ammonia that protects the bacterium in the acid environment of the stomach. The ammonium ions produced can be toxic to the gastric superficial epithelial cells. Urease stimulates inflammatory cytokine production and activates mononuclear phagocytes. Although, after colonisation, the host immune defences are stimulated, and there is increased secretory IgA (sIgA) detected in the gastric mucosa and raised specific IgG, while the infected host is not able to eliminate the organism. Colonisation results in persistent gastric inflammation but the clinical course of infection can be very variable[9].
2 Current treatment of H. pylori infections
The treatment for eradication of H. pylori is complicated, requiring a minimum of two antibiotics in combination with gastric acid inhibitors. Although H. pylori is sensitive to many antibiotics in vitro, no single agent is effective alone in vivo. Firstly, the bacterium resides below the gastric mucus adherent to the gastric epithelium and thus access of drugs to this site is limited. Secondly, the strain may have acquired resistance to the commonly used antimicrobial drugs[10]. These infections are currently treated with a firstline triple therapy treatment, consisting of one proton pump inhibitor (PPI) and two antibiotics. None of the antibiotics used achieves sufficient eradication when used alone and also require adjuvant therapy[11]. This consists of agents increasing pH within the stomach to allow local action of antibiotics not active at low pH, and PPIs are used at a dose equivalent to 20 mg omeprazole twice daily. It was suggested that ranitidine bismuth citrate (RBC) regimens may be less influenced by antibiotic resistance than PPIbased therapies[12].
The most effective therapies combine two antibiotics including clarithromycin and amoxicillin with a gastric acid inhibitor. However, increasing resistance to current antibiotics is driving research to produce alternatives to the commonly used therapies. In addition to increasing levels of antibiotic resistance, the hostile environment of the stomach, reducing antibiotic bioavailability at the site of action, contributes to failures in treatment[13]. Current recommended regimes are not wholly effective, for example, triple therapy with bismuth, metronidazole and amoxicillin or tetracycline has an eradication efficiency of 60%80%, and patient compliance, sideeffects and bacterial resistance can be problematic with this regime[14]. Alternatives proposed include quadruple therapies, based on, for example, colloidal bismuth subcitrate, tetracycline, metronidazole and omeprazole[15]. Patient compliance with such a complicated dosage regime could be improved by combining the therapies in a single dosage form, and a capsule containing bismuth biskalcitrate, metronidazole and tetracycline (Helicide) has been developed in an effort to improve patient compliance and has currently received approval[16]. There is concern regarding acquired resistance to two of the commonly prescribed antibiotics: clarithromycin and metronidazole. Although not as widespread, resistance to metronidazole can also be problematic but it can be overcome in some cases by lengthening the duration of treatment[17].
3 Drug delivery systems for gastric retention
Major problems in the eradication of H. pylori are the presence of antibioticresistant bacteria requiring multiple drugs with complicated dosing schedules and bacterial residence in an environment where high drug concentrations are difficult to achieve. In order to ensure that the therapy is adequately delivered to the unique niche of the gastric mucosa, development of oral dosage forms with prolonged gastric residence is desirable. Gastric retentive delivery systems have been studied for a number of years, and generally requirements of such strategies are that the vehicle maintains a controlled release of drug and exhibits prolonged residence time in the stomach. Overcoming the physiological barriers of the human GI tract is a major challenge facing successful development of gastric retentive systems and leads to problems with reproducibility. In addition to the thick protective mucus layer, gastrointestinal motility patterns are another obstacle facing drug delivery to the stomach. In the fasted state, the interdigestive myoelectric motor complex (IMMC) is a 2hour cycle of peristaltic activity that regulates motility patterns[18]. Phase Ⅲ of the IMMC is also called the housekeeper wave and consists of strong, intense contractions designed to remove debris such as undigested food from the stomach[19, 20]. Gastric residence time will depend on which phase of IMMC is active. In the fed state, the stomach churns food to sizes less than 1 mm, which is then emptied to the duodenum. Type of the food determines its residence time in the stomach with liquids emptying rapidly and solids much more slowly. Gastric residence time is generally longer in the fed rather than fasted state. The gastric residence time of dosage forms is also influenced by posture, age, gender, disease status and concomitant medication. A number of different techniques have been explored to increase gastric retention including high density and magnetic systems, but the three main systems are floating systems, bio/mucoadhesive systems and swelling systems.
4 Floating drug delivery systems
Various approaches had been made since the late 1970s to utilise floating behaviour in order to prolong residence. Designs include hydrodynamically balanced systems (HBS), microspheres, gasgenerating systems and raftforming systems. Originally, such systems were proposed to reduce fluctuations in drug levels and provide sustained release as the duration of most oral sustained release preparations is 812 hours, due to a relatively short GI transit time[21, 22]. HBS has a bulk density lower than gastric fluids and contain one or more colloids formulated into a single unit with the drug and other additives, which swell on contact with water and facilitate floating[23, 24]. A density of less than 1.0 g/mL is required. A triplelayer floating tablet system was proposed containing a swellable gasgenerating layer, a swellable drugcontaining layer (with tetracycline and metronidazole) and a rapidly dissolving layer containing bismuth salts. The system was capable of providing sustained release of the antibiotics in vitro at pH 1.8 and demonstrated buoyancy in vitro, however no in vivo results are reported. Tablets containing a 1︰2 ratio of hydroxypropylcellulose to amoxicillin, with a gasgenerating system, failed to improve efficacy. These large singlelayer tablets remained buoyant in vitro but bioavailability was reduced to 80.5% as compared with conventional capsules in fasted humans[25]. Intersubject variability in gastric transit times with floating tablets and HBS results in unreliable and irreproducible residence times in the stomach and remains a significant problem with such systems. This can be addressed by using multipleunit pided systems such as microspheres. As these can spread evenly through the stomach contents, they can avoid the problems of variable and early gastric emptying or bursting associated with the singleunit systems. Polymers used in formulation of floating multipleunits include caesingelatin acrylic polymers such as Eudragits and alginates[26]. Alginic acid is a polysaccharide consisting of Dmannuronic acid and Lguluronic acid. It forms a bioadhesive and stable gel with palent cations such as calcium and the sodium salt been used in a variety of oral and topical formulations. Floating alginate systems such as Gaviscon form a buoyant gel which floats on the gastric contents alleviating symptoms of heartburn. Its stability in acidic media has made it a popular choice for gastric retentive delivery systems. For example, floating multiple units consisting of a calcium alginate core, separated from a calcium alginate/polyvinyl alcohol (PVA) membrane by an air compartment displayed prolonged gastric retention after a meal. Alginate beads are commonly prepared by extruding alginate, dropwise, into a solution containing Ca2+. The resultant beads are porous and can be used to encapsulate a variety of drugs with a wide range of physicochemical properties[27]. Adequate control of drug release from such formulations often requires some modification to the matrix. For example, foambased floating microspheres can be prepared by adding polypropylene foam powder to an organic solution containing dissolving polymer (Eudragit RS or polymethyl methacrylate, PMMA) and drug. Upon solvent evaporation, freeflowing microspheres are formed with extended release profiles[28]. Two types of alginate floating beads containing metronidazole were compared; one formulation contained chitosan and the other contained vegetable oils. In vitro release was complete from all formulations within two hours. Following administration to guinea pigs, it was concluded that after three hours chitosancontaining particles resulted in increased drug levels in the gastric mucosa as compared with metronidazole solution[29]. A multipleunit floating dosage form formulated using calcium alginate was prepared by dropping sodium alginate solution into calcium chloride and the resultant particles were freezedried. Amoxicillin was incorporated into these beads by addition of drug to the calcium chloride solution. Once the sodium alginate was extruded into the solution, the resultant gel beads were left for thirty minutes before extraction and freezedrying. Amylose was also added to the formulation in an attempt to reduce the release rate. Amoxicillin release showed an initial burst effect and the release was described by Higuchi kinetics, implying that it is controlled by diffusion of the drug through a porous matrix. Gammascintigraphic studies showed evidence of gastric retention of the floating beads in all seven subjects even following normal food intake.
A major limitation with such systems is the requirement for sufficient volumes of gastric acid within the stomach to enable the devices to float. It may be that using a single approach to localise delivery in the stomach may not be sufficient to resist the forces of gastric emptying. It was therefore envisaged that a floating dosage form with mucoadhesive polymers could extend the period of gastric retention, exploiting the retentive properties of the floating system and the ability of bioadhesive formulations to adhere to inflamed tissue. Floating, bioadhesive microsphere systems containing acetohydroxamic acid (AHA), a cytoplasmic urease inhibitor, were prepared. A solution of AHA and the acrylic polymer (Eudragit E) in ethanol/dichloromethane was added to an aqueous PVA solution to form an oilinwater emulsion. The drug and polymer precipitated due to preferential diffusion of ethanol into the aqueous phase. After evaporation of the dichloromethane, the particles were dried and an air cavity was produced inside the spheres giving the particles the ability to float[30]. These particles were spraycoated with the mucoadhesive polymer, polycarbophil. Floating ability was demonstrated in vitro and demonstrated greater percentage growth inhibition of H. pylori in vitro than free drug. Release rates were extended due to the polycarbophil coating[31]. Similar preparations using polybisphenolA carbonate as the coating polymer also showed buoyancy, extended drug release and inhibition of growth of H. pylori in vitro. Clearance of an inoculated strain of H. pylori from the stomach of gerbils following oral delivery of the encapsulated drug was shown to be better than free drug, presumably due to better retention. Although AHA has been shown to be effective at reducing gastritis in a Mongolian gerbil model, further studies are needed to prove that established antibiotics could also be successfully encapsulated into, and released from, such formulations and their efficacy demonstrated in human models[30].
5 Herbal and integrative drugs against H. pylori infections
5.1 Black myrobalan The aqueous extract of black myrobalan (Terminalia chebula Retz) has been shown to have uniform antibacterial activity against ten clinical strains of H. pylori[32, 33]. This activity was bactericidal after 3 h and was stable after autoclaving. Although Sato and coworkers[34] reported gallic acid and ethyl gallate in T. chebula Retz and have shown antibacterial activity of ethanol extracts of this plant against both methicillin resistant and sensitive Staphylococcus aureus and other bacteria, the components of T. chebula Retz aqueous extracts responsible for the observed bacteriocidal activity remain unknown[35]. The antibacterial activity of aqueous extracts of black myrobalan against H. pylori was significantly higher than that of ether and alcoholic extracts. The aqueous extract preserved its antibacterial activity after autoclaving for 30 min at 121 ℃ and was inhibitory at 125150 mg/L. When the plant powder was tested directly against H. pylori, without grinding and (or) extraction and using Colombia Agar plates, the mean inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were 150 and 175 mg/L, respectively.
5.2 Ginger Ginger root (Zingiber officinale Rosc.) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness, dyspepsia and hyperemesis gravidarum, and is also reported to have chemopreventative activity in animal models[36]. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since H. pylori is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the antiH. pylori effects of ginger and its constituents were tested in vitro[37]. A methanol extract of the dried powdered ginger rhizome, fractions of the extract and the isolated constituents, 6, 8 and 10gingerol and 6shogoal, were tested against 19 strains of H. pylori, including 5 CagApositive strains. The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a MIC range of 6.25 to 50 μg/mL. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all H. pylori strains with an MIC range of 0.78 to 12.5 μg/mL and with significant activity against the CagApositive strains. These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagApositive strains in vitro and this activity may contribute to its chemopreventative effects[38].
5.3 Turmeric Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa L.), has been shown to prevent gastric and colon cancers in rodents[39]. Many mechanisms had been proposed for the chemopreventative effects, although the effect of curcumin on the growth of H. pylori has not been reported. H. pylori is a group 1 carcinogen and is associated with the development of gastric and colon cancer. A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H. pylori, including 5 CagApositive strains. Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 6.2550 μg/mL. These data demonstrate that curcumin inhibits the growth of H. pylori CagApositive strains in vitro, and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects[40, 41].
5.4 Thyme A popular herbal remedy in ancient Egypt, Greece and Rome, thyme was mainly used for headaches, digestive problems, respiratory illness, and as a moodenhancer. Researcher who investigated the antimicrobial properties of 21 essential oils against five important foodborne pathogens, including Escherichia coli (E. coli) noted that thyme was very effective at inhibiting the bacteria. Thyme extract was compared with several antibacterials; it had a significant inhibitory effect on H. pylori[42].
5.5 Licorice In a recent study at the Institute of Medical Microbiology and Virology, Germany, researchers found that licorice extract produced a potent effect against strains of H. pylori that are resistant against clarithromycin, one of the antibiotics typically used in the three antibiotic treatment regimens[43]. The authors concluded that this study provides hope that licorice extract can form the basis for an alternative treatment for H. pylori infections[44].
5.6 Berberine Berberine is a plant alkaloid isolated from the roots and bark of several plants including golden seal, barberry, Coptis chinensis Franch. and Yerba mansa. Berberinecontaining plants have been used medicinally in ayurvedic and Chinese medicine, and are known to have antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. More recently, berberine had been demonstrated to be effective against H. pylori[45].
5.7 Goshuyn (Evodia rutaecarpaa Chinese herb) After testing no less than 113 Chinese herbs for antiH. pylori activity in vitro, Japanese researchers identified goshuyn (Evodia rutaecarpa) as the most effective medical plant. Subsequently, they conducted a randomised clinical trial of two synthetic antibiotics versus the same combination plus goshuyn. The eradication rates were 60% and 80%, respectively[46].
5.8 Other Chinese herbals In an animal study or bacteriostatic test of 53 Chinese herbs, Zhang et al[47] found Coptis chinensis, Rheum palmatum, Panax notogenseng and Magnolia officinalis were effective against H. pylori. Prunus mume and Corydalis yanhusuo were moderate effective.
6 Conclusion
The gastric retention approaches as well as herbal drugs described here have applications for treatment of H. pylori infection although further development is required for each to be fully effective, especially in human studies. Overcoming the high mucus turnover rate and resulting limited retention times is a challenge for bioadhesive systems, and swelling systems must guarantee clearance from the stomach after a certain time to prevent any obstruction. The lack of availability of biocompatible chemical cross linking agents is a major stumbling block in the development of covalently crosslinked hydrogels. Floating systems are available commercially, and combination approaches, using floating behaviour and mucoadhesion, have also shown promise. Exploiting dual mechanisms of retention may provide the strength and reproducibility required to permit successful advancement in this field. So in future, a combination of herbal drugs with the novel drug delivery systems mentioned above, may lead to an important breakthrough in the herbal/integrative treatment of H. pylori infections.
7 Acknowledgement
I would like to acknowledge Dr. K. Pundarikakshudu for giving constant help to compile the information and in preparation of this article. I am also very much thankful to Prof. B.M. Peerzada and Prof. Manish Shah for constant encouragement.
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