Nataša Bijelic Ćesi

Sex Education in Croatia Tensions between Secular and Religious Discourses

Keywords:

This article explores the influence of the Catholic church on educational policy, more specifically on sex education, in Croatia. It explores tensions between secular and religious discourses regarding the introduction of a sex education programme supported by the Catholic church into Croatian schools. The presence of the Catholic doctrine in the educational system provided the basis for the introduction of sex education with a religious framework, namely the GROZD sex education programme. The GROZD (Glas roditelja za djecu [Parents' Voice for Children]) programme triggered a public discussion that soon became a polarization between liberal (i.e. secular) and traditional (i.e. religious) discourses. In the discussion, the traditional/Catholic value system was used as a justification for the introduction of a sex education programme that was seen by opponents as harmful.

INTRODUCTION

In the Catholic tradition, terrestrial life is treated as having secondary importance because Catholics should endure suffering in the hope of heavenly reward. On the other hand, earthly church institutions have developed a concomitant interest in any temporal matter that affects the church's institutional interests (Ramet, 1990: 3). This insightful comment about the duality of the Catholic tradition is also applicable to the Croatian context. One of the Catholic church's historical interests is in the regulation of sexuality [START_REF] Weeks | Sexuality and the Historian[END_REF]. In Croatia, one of the ways this interest has materialized is through the introduction of a sex education programme into schools.

A number of research projects and analyses have supported the argument that after the demise of socialism in 1990, the public role and influence of the Catholic church increased in Croatia [START_REF] Borowik | Religion and Patterns of Social Transformation -or How to Interpret Religious Changes in Post-Communism?[END_REF][START_REF] Vrcan | Torn Between Tremendous Challenges and Tormenting Responses: Religion in the Nineties in the Area of Former Yugoslavia[END_REF][START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. The focus of this article is not the privileged position of the Catholic church since 1990 because that would call for a detailed analysis beyond the scope of this text. Rather, I focus on one of the consequences of such a privileged position, namely the church's influence on educational policy -more specifically on sex education. This article explores the tensions between secular and religious discourses regarding the introduction of a sex education programme supported by the Catholic church into schools. It starts by outlining the presence of the Catholic doctrine in the educational system, which provided the basis for the introduction of sex education within a religious framework -namely the GROZD (Glas roditelja za djecu [Parents' Voice for Children]) sex education programme. The GROZD programme triggered a public discussion, which soon became dominated by a polarization between liberal (i.e. secular) and traditional (i.e. religious) discourses. The traditional/Catholic value system was used to justify the introduction of a sex education programme that its opponents believed would cause harm.

The perspective of this article is affected by my own specific positioning within the process: first, as a member of the expert group that proposed a liberal programme of sex education and, second, as a member of a civic coalition that advocates against the discriminatory and religiously based GROZD programme being taken up in schools.

THE CATHOLIC DOCTRINE IN THE EDUCATIONAL SYSTEM

The privileged status enjoyed by the Catholic church in Croatia, here understood as an institution with a structure and hierarchy, was established by a series of international agreements that the Republic of Croatia signed with the Holy See. The four agreements were signed in 1996 and 1998. The agreements were prepared secretly, without public knowledge or discussion, and after being signed entered parliamentary procedure [START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. The Agreement on Cooperation in the Field of Education and Culture is especially important for this discussion because it ensured the privileged position of the Catholic church in the educational system. This agreement states that the values of Christian ethics have to be taken into consideration in the whole educational system, i.e. in all public kindergartens, schools and universities (Zrinšc ˇak, 2004: 309); this includes the teaching of the Catechism in pre-schools, elementary and secondary schools. 1 In 1999, Catholic dogma was introduced into the educational system through the teaching of the Catechism in kindergartens and the state schools. The decision to introduce Catholic instruction was a government decision made without any public or parliamentary debate [START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. Around 90 percent of pupils in elementary school attend Catholic instruction and 75 percent in secondary schools [START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. The introduction of Catholic instruction and the Catholic monopoly in education raised concerns about the division of children of different confessions as well as children who are non-believers, but these arguments were completely disregarded (Zrinšc ˇak, 2004: 309). In elementary school, pupils who do not want to attend religious education are free for that school hour. Elementary schools, however, do not offer an alternative subject for pupils while their peers are attending Catholic instruction. The social pressure on these children, although not documented, is high. In order to fit in (or because they have no other place to go), these children often end up in a religious education class despite not being believers. 2 In secondary school, pupils can choose between a subject called 'ethics' and Catholic instruction.

Moreover, Vatican treaties violate the constitutional provision that all religious communities shall be equal before the law [START_REF] Padjen | The Status of Minor Religious Communities in Croatia: A Revival of Legal Pluralism[END_REF]. These agreements have precedence over national law 3 and all international human rights conventions that the Republic of Croatia has ratified. Consequently, international human rights conventions, including those relevant to the protection of reproductive and sexual rights, have less legal power than the agreements concluded with the Holy See (Škrabalo and Juric ´, 2005: 179).

Catholic teaching on human sexuality and reproduction is unambiguous and is a part of Catholic instruction. 4 The church advocates the protection of human life from conception and is opposed to abortion. It approves sexual activity only within heterosexual marriage and is against mechanical or chemical contraceptives. Homosexuality is viewed as incomplete sexual orientation and to practise homosexual behaviour is seen as sin. Simultaneously, international human rights treaties, ratified by Croatia, provide the legal foundation for the right to sex education that should be accurate and objective and free of prejudice and discrimination (Zampas and Kebriaei, 2007: 4). Additionally, some national policies also oblige the state to introduce accurate sex education free of discrimination. Consequently, this leads to a discrepancy in the educational system. This discrepancy enables the parallel existence of a sex education programme based on religious and secular teaching. Thus, we have the juxtaposition of Catholic teaching on sexuality ensured through Vatican agreement and secular teaching ensured through human rights treaties and national legislation. This juxtaposition has produced tensions between secular and religious discourses regarding the introduction of sex education. Agreements with the Vatican are concordats, which according to Padjen (2004: 104) are international legal acts sui generis in several respects: the Catholic church as one of the concordat parties is neither a nation-state nor an international organization; a concordat is not registered with the UN secretary general and since a concordat involves divine law, the Holy See is not in a position to accept the decision of a third party, even if it were an international court or tribunal, for the settlement of disputes. Having in mind the legal force of the Vatican agreement, Catholic instruction and its teaching on sexuality is almost impossible to eliminate from the educational system. Undoubtedly, Catholic instruction in schools has laid down the foundations for the introduction of religiously based sex education.

THE PROBLEMATIC CONTENT OF THE GROZD PROGRAMME -THE MODULE ON HUMAN SEXUALITY

The latest programme backed by the Catholic church directly promoting Catholic morals and values regarding sexuality is the programme offered by the GROZD Association. In 2006, the GROZD Association presented three experimental programmes on health education: 5 health education for elementary schools, for the three-year secondary schools 6 and for high schools. These programmes contain a module on human sexuality that ignores scientific facts and offers a value system that places sexual intercourse in the domain of heterosexual marriage and procreation. The human sexuality and sex education values supported by GROZD are love, restraint (until marriage) and faithfulness (Udruga GROZD, 2006a: 10;2006b: 10;2006c: 10).

By claiming that 'human sexuality represents a gift' that can reach its real purpose 'through the gifts of love between two persons of different sex' (Udruga GROZD, 2006a: 10;2006b: 10;2006c: 10), GROZD promotes a particular value system that is in accordance with the Catholic doctrine (Katekizam katolic ˇke crkve [Catechism], 1994: 573-87) and not with the socially accepted values of the Republic of Croatia such as freedom and gender equality (Constitution of the Republic of Croatia, Art. 3). Most of the subjects taught in the GROZD programme are related to Catholic instruction, which is a part of the curriculum.

The programme's methodology proposes 'separate classes for male and female students' and that male and female students should learn about both genders but in 'different scope and order', meaning that, for example, young men should learn more about young men (Udruga GROZD, 2006a: 20;2006b: 20;2006c: 20). This methodological recommendation restricts information to young people and therefore violates their right to complete information regarding sexuality.

The theme of masturbation is presented according to Catholic teaching, stressing the need to 'develop the ability to control one's sexual excitement and the capability to overcome the possible habit of masturbation' (Udruga GROZD, 2006a: 33;2006b: 33;2006c: 73).

The themes of contraception and abortion are unacceptably dealt with from the standpoint of women's human rights, gender equality or medical science. This programme teaches that there is no safe sex and provides information only on natural contraception (never mentioning condoms) and falsely claiming that 'contraceptives change the essence of the sexual intercourse because they don't respect the complete nature of the relation between man and woman, which is complicated, yet fascinatingly harmonious' (Udruga GROZD, 2006b: 72;2006c: 59). By presenting valueoriented statements closely related to Catholic doctrine, the GROZD programme is potentially placing young people, especially young women, in danger and once again is violating their right to accurate, complete and scientific information on sexuality and reproductive health.

Regarding the issue of abortion, GROZD represents the stand taken by the Catholic church. The programme teaches that 'when thinking about abortion, the solution that goes against life is never and for no one the "only" or a good solution' (Udruga GROZD, 2006b: 61;2006c: 62). This teaching is in contradiction to Croatian law and international standards of reproductive rights and health because it restricts women's reproductive rights and advocates a ban on abortion. This teaching is not only illegal but imposes a religious worldview on young people attending state schools while the data from public opinion surveys support the secular attitude to abortion: 65 percent of the Croatian population support women's right to abortion [START_REF] Gfk | Slic ˇice iz istraz ˇivanja javnog mnijenja[END_REF].

Teaching on sexual intercourse offers a religious view on the subject by stating that 'sexual intercourse represents the physical part of one person's devotion to another and that using sexual intercourse for pure fulfilment of attraction makes a person less capable of real, original devotion' (Udruga GROZD, 2006a: 75). Simultaneously, by also stating that 'sexual intercourse . . . achieves its full purpose in a complete relationship based on love between man and woman living in a lasting community of faithfulness (marriage)' (Udruga GROZD, 2006b: 49;2006c: 49), this religious view openly discriminates against gays and lesbians. Additionally, a statement such as 'homosexual intercourse stands against the very nature of sexual intercourse' (Udruga GROZD, 2006b: 46;2006c: 46) serves to perpetuate homophobia in the educational system.

The GROZD programme also discriminates against any form of family life that is not based explicitly on heterosexual marriage. Teaching that 'the reasons for divorce often lie in the wrong motives for entering marriage and in the bad predispositions of persons entering marriage, i.e. their inability for real love' (Udruga GROZD, 2006b: 61;2006c: 62), the programme discriminates against persons who are cohabitating or are divorced, and also against their children.

THE INTRODUCTION OF SEX EDUCATION INTO CROATIAN SCHOOLS

The national curriculum for primary and secondary schools had not included mandatory and comprehensive sex education. Instead, there were some extra-curricular programmes implemented by various non-governmental organizations and health clinics (e.g. the Teen STAR programme, MEMO AIDS programme). The process of introducing sex education into Croatian schools began in 2005. A year before, the Catholic church had stepped up the pressure for the introduction of sex education based on religiously acceptable principles. The following examples outline the controlling position that the church has in the educational system and demonstrate the strong impact the Catholic worldview has on educational policy.

Through Catholic teaching, the church is directly involved in the educational system but it also has an indirect influence on educational policy. The indirect influence of the church is illustrated by the example of the unsuccessful attempt to introduce the MEMO AIDS 7 programme into schools. In 2004, the church publicly condemned MEMO AIDS, in particular attacking the programme for its recommendation that secondary school students be taught about condom use. Condoms were considered by the church to be insufficiently reliable and ethically unacceptable for HIV/AIDS protection. MEMO AIDS was intended to be introduced as an optional programme into a substantial number of secondary schools in Croatia, with the support of the Ministry of Health and the UN's Global Fund. After the church's reaction, there was a drop in schools' take-up of the programme. One statement from the church was enough to influence the behaviour of a number of head teachers (Škrabalo and Juric ´, 2005: 197).

Another example was the public scandal that emerged in 2004 over the showing of the American documentary Silent Scream during a Catechism lesson in one secondary school in Zagreb. The documentary contains scenes of foetus curettage at the later stage of pregnancy and represents an example of anti-choice propaganda. The Ministry of Education concluded that the film was unsuitable as educational material. The minister informed the Cardinal of the Catholic church about the decision, and the Cardinal concurred. Only after consensus with the church was reached on the case, were schools informed about unsuitability of the film for educational purposes (Škrabalo and Juric ´, 2005: 187).

That same year, civil society organizations were the first to criticize and draw public attention to the Teen STAR programme and initiated legal and advocacy initiatives to urge reform of its problematic content. Teen STAR 8 is a government-approved extra-curricular sex education programme. It is an abstinence-based programme supported by the Catholic church. It has been taught in a small number of primary and secondary schools. The action against Teen STAR included complaints to the Offices of the Ombudspersons for Children's Rights and for Gender Equality, who were both highly critical of the programme. They found several aspects of the Teen STAR programme to be in violation of the Croatian constitution, national laws such as the Gender Equality Law and the Law on Same-Sex Communities and the Convention on the Rights of the Child and the Universal Declaration on Human Rights.

In a social atmosphere where Catholic morals and values are directly or indirectly part of the educational system, the Ministry of Education decided, in light of these events, to resolve the problem and tackle the issue of sex education. For that purpose, a number of various experts were engaged and two committees were formed. During this process, tensions between secular and religious discourses emerged. In the first committee, members of the Catholic church were overrepresented. The committee proposed the introduction of a health education programme into schools. This proposal was obviously a compromise between the liberal (i.e. more secular) and conservative (i.e. more religious) members of the committee. The liberal members concluded that for the purposes of overcoming the ideological tensions that existed among committee members, the best would be a compromise solution, i.e. health education.

The second committee decided that the GROZD programme should be introduced into schools, providing they change the sex module. GROZD never did introduce changes; moreover the Ministry requested that the committee reconsider approving the GROZD programme without revision.

REACTIONS AGAINST THE GROZD PROGRAMME

The decision to introduce the GROZD programme into schools triggered an immediate reaction from civil society organizations, who were later joined by other protagonists in the public debate. There was a juxtaposition of secular and religious discourses in the public debate. Representing the secular side were the Civic Coalition to Stop High-Risk Sexual Education and the Ombudspersons for Children's Rights and for Gender Equality. On the other side were the GROZD Association and the Catholic church.

The Civic Coalition to Stop High-Risk Sexual Education was established at the beginning of 2007 as a direct consequence of the Ministry of Education's decision to introduce the GROZD programme as a pilot into schools for the school year 2007/8. The Civic Coalition is an advocacy network of some 130 civil society organizations, networks, institutions and 350 individuals concerned with issues of human rights, sexual and reproductive health and the rights of youth and gender equality. The Coalition has denounced the GROZD programme as unacceptable because it promotes attitudes on human sexuality that are contrary to modern scientific findings, that breach Croatian constitution and laws, are not in the interests of public health and violate international human and gender equality rights. The Coalition advocates that the GROZD sex education pilot programme be halted. Another of its goals is to stop the implementation of an unsuccessful public policy on the reproductive and sexual health rights of young people that the Croatian government has been promoting since 2005 (Civic Coalition to Stop High-Risk Sexual Education, 2007). Finally, the Coalition advocates for the implementation of a single, standardized education programme on human sexuality based on scientific facts and in accord with international conventions and treaties. It is important to stress that the Coalition as an advocacy network does not have its own proposed sex education programme.

The Ombudspersons for Children's Rights and for Gender Equality issued statements to the Ministry of Education criticizing the sex education component of the GROZD programme. The Ombudsperson for Children's Rights asserted that the programme's portrayal of marriage as the preferred partnership and its negative depiction of divorce do not comply with Croatia's Family Law but are discriminatory. She also noted that the GROZD programme presented value-laden messages about homosexuality, as opposed to developing children's ability to understand the diversity of values, and to then make their own independent decisions. She noted that parts of the GROZD programme are not scientifically based, and, as a result, violate Croatia's own national curriculum policy (Office of the Ombudsperson for Children, 2007).

The Ombudsperson for Gender Equality asserted that the programme's sex education component violated Croatia's law on gender equality and discrimination on the basis of gender, marriage, family status or sexual orientation. Specifically, she noted that the GROZD programme failed to distinguish between sex and gender roles, thus potentially hindering the elimination of stereotypes. In her opinion, the programme's teaching on the true meaning of intercourse in heterosexual marriage discriminates against unmarried people and divorced people, and children born out of wedlock, and violates Croatian constitutional and statutory gender equality protection. Another of the programme's doctrines, that homosexual acts are unnatural, she interpreted as discriminatory and in violation of Croatia's Same Sex Union Law, which prohibits discrimination on the basis of same-sex unions and/or homosexual orientation (Office of the Ombudsperson for Gender Equality, 2007).

The teachings of the GROZD programme transgress sexual and reproductive rights by restricting access to accurate and complete information regarding sexuality issues. It ignores gender relations and gender roles that women are forced to perform and discriminates against homosexual sexual relations. Anti-choice teaching on abortion undermines women's autonomy and life choices, and also their right to equality. The programme ignores the prevalence of violent sexual intercourse that women are often subjected to. Promoting heterosexual marriage is discriminatory because it places women in only one possible type of relationship and thus discriminates against women who live in non-married relationships or homosexual relationships or who are single and also discriminates against the children of single-parent families. Also discriminatory is the characterization of persons who divorce as incapable of real love. This reinforces women's unequal status, and ignores the fact that women also divorce because they are the victims of domestic violence [START_REF] Zampas | Experts' Comments on GROZD Programme[END_REF]. Despite the negative reactions to the programme, the Ministry proceeded to approve its implementation in schools.

TENSIONS BETWEEN SECULAR AND RELIGIOUS DISCOURSES IN THE PUBLIC DEBATE

Religious/traditional discourse is influenced by nationalism and intersects with the Catholic church and its religious values. This symbiosis of religion and nationalism is the product of Croatia's recent past. During the Communist period there was a rigid separation of church and state. Religion was considered as non-progressive and often belonging to the private sphere [START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. The strong tide of secularism was a direct consequence of this period. After the political changes in 1990, when the first democratic elections were held, the status and the role of the church and relations towards religion changed drastically. The new nationalist political system formed a special bond with the Catholic church [START_REF] Mirescu | Religion and Ethnic Identity Formation in the Former Yugoslavia[END_REF]. The Catholic church became a symbol of national identity and religion was used for political purposes, while politics became influenced by religion [START_REF] Vrcan | Torn Between Tremendous Challenges and Tormenting Responses: Religion in the Nineties in the Area of Former Yugoslavia[END_REF]. Religion served to strengthen nationalist/ethnic identity, a factor supported by the historical role of the Catholic church in maintaining the separate Croat identity [START_REF] Zrinšc ˇak | Religion and Society in Tension in Croatia[END_REF]. Secular and religious discourses are characterized by different social values and political positions. Representatives of the religious discourse hold more traditional values, which include patriarchal, authoritarian, ethnocentric and national features, while representatives of the secular discourse hold more modern, liberal values and support gender equality and nondiscrimination [START_REF] Labus | Vrijednosne orijentacije i religioznost[END_REF].

Feminist theorizing considers sex education to be a domain regulated and controlled by men, where sexual knowledge is the outcome of a maledominated society [START_REF] Jackson | Heterosexuality in Question[END_REF][START_REF] Lees | Sugar and Spice: Sexuality and Adolescent Girls[END_REF]. The GROZD programme represents a conservative approach to sex education and as such is concerned with morality, religious values, ideals of family life and a patriarchal gender order [START_REF] Lees | Sugar and Spice: Sexuality and Adolescent Girls[END_REF]. In the GROZD sex education programme, where Catholic sexual norms are dominant, a relationship between sexuality, cultural tradition and gender is being reproduced. A naturalized gender order is an integral part of the programme and the role of gender here is to control female sexuality. Moreover, the GROZD Association considers gender to be a 'feminist fabrication' (Kalogjera Brkic ´, 2007a). 9 In the public debate surrounding sex education, the religious discourse stressing traditional values predominated, while the secular discourse stressing the provision of accurate and value-free information on sexuality and respect for sexual/reproductive rights became largely invisible. Feminists have argued that the regulation of women and their sexuality often stands for national culture (Yuval Davis, 1997: 22). The restrictive nature of GROZD's teaching on sexuality can be equated with national tradition and culture. For GROZD, national culture comprises strong national and patriarchal features. The GROZD Association considered traditional values to be crucial in sex education. In its support, the association mobilized Croatian academics and doctors of science, who signed a statement stating that health education needs to be value oriented. More specifically, 'values such as marriage, family and respect of parents have to be part of the programme because these values are important to Croats' [START_REF] Glavina | Zdravstveni odgoj: 255 uglednika potpisalo izjavu u kojoj podrz ˇava Grozdov program[END_REF].

A particular traditional/religious value system is employed as a justification for specific teachings that control female sexuality and reinforce gender inequalities. Human rights are considered by some to be the imposition of external values that strip societies of their cultural identity (Kim, 1993: 59), and such a view was shared by religious circles in the public debate on sex education.

The public debate on sex education programmes was a discussion about values. Values had a central place in this debate because the polarization between the conservative and liberal stance with regard to sex education was constantly stressed. 10 According to GROZD, values are the lynchpin of its sex education programme because in the organization's view every sex education programme in schools should respect the value system of the parents and also the value system and cultural context of the country ('Health/Sex Education for Schools -The Situation in Croatia ', 2007); the programme is supported by all major religious communities in Croatia. The GROZD Association emphasizes education that supports values and states that the parents themselves have the right to choose the programme they want their children to follow.

Like the GROZD Association, the Ministry of Education also asserted that a sex education programme is a private matter for parents. Parents ought to be able to choose for their children between a traditional and liberal programme according to their values. Feminist theory recognizes such a public/private distinction as problematic. The private domain is often understood as one of individual interactions and interpersonal relations, while the public domain is a domain of institutions (Kim, 1993: 66-7). The decision to introduce sex education is the responsibility of the Ministry, i.e. the public domain, but simultaneously this responsibility is shifted to parents, i.e. to the private sphere. The notion of sex education as a private matter served as justification for introducing a programme that reinforces gender inequalities. Using the patriarchal public/private divide, the Ministry of Education has invoked cultural tradition to support gender inequalities through the sex education programme. The public/ private distinction has entered into the public debate as a justification for state non-intervention because the decision on a sex education programme is considered to be part of a society's culture.

On the opposite side to this was a discourse on human rights neither as visible nor as powerful in the public discussion on sex education. In this approach values are not the central concern. This discourse is concerned with providing value-free information in order to respect, protect and fulfil the human rights of young people. The human rights discourse was invisible in the public debate because it was equated with the liberal value orientations of its protagonists. What was missing in the debate, however, was the fact that sexual and reproductive rights are embedded in the legal system and therefore do not just represent the liberal value orientations of some of the protagonists in the debate.

The GROZD Association stated that their programme was being attacked by the radical homosexual and feminist lobby, which declared their values to be scientifically unfounded and illegal ('Health/Sex Education for Schools -The Situation in Croatia', 2007). In addition, Catholic circles stated that 'at the moment when a loud minority, no matter what their goals are, impose their values on the majority, it is necessary to shake up the sleepy majority' [START_REF] Baloban | Raskorak izmed ¯u ideala i konkretnoga z ˇivota[END_REF]. The value system of the 'majority', i.e. the Catholic value system, was being utilized as justification for GROZD's discriminatory teaching on sex. This demonstrates how their religious discourse was being presented as dominant and thus more valid in the public debate.

The Catholic church even denounced the involvement of the Ombudsperson for Children's Rights in a public discussion about health education as inappropriate (Pavic ˇic ´, 2007) and thus undermined the importance of the rights approach. Reactions from the state institutions to the Ombudsperson's complaints showed a bias towards the religious stance. An adviser to the Minister of Education stated, just like the GROZD supporters, that it was quite clear that the GROZD programme did not violate anyone's constitutional rights (Kalogjera Brkic ´, 2007b). Furthermore, the Minister of Health stated that he would not take into account the opinion of the Ombudsperson for Children's Rights because she was not a medical doctor and thus displayed a total ignorance with regard to the decision-making process on sex education (Kustura, 2007).

A focus on youth themselves was also missing from the public debate. On the level of values, young people who nevertheless consider them-selves to be religious have in fact opposing attitudes on sexuality to those propounded by their religion and church (Marinovic ´ Jerolimov, 2002: 123). The existence of secular values and attitudes regarding sexuality among religious youth offers a different perspective on the GROZD concept of sex education. This discrepancy may suggest that religiously based sex education that targets religious youth will not be effective.

CONCLUSION

This examination of the proposed introduction of the GROZD programme demonstrates how the influence of the Catholic church in an educational system can be repressive in relation to the sexual and reproductive health and rights of youth. By engaging with a particular value system sexual and reproductive rights are violated. This discriminatory teaching has been justified by the claim that sex education should respect the value system of the parents and the cultural context of the country. By invoking tradition and the religious value paradigm, GROZD has reinforced gender inequality, simultaneously undermining the concept of human rights in the public debate. There has been a strong tendency, even pressure, for educational policy to be consistent with the opinions of the Catholic church. The final decision by the Ministry of Education on the actual implementation of the GROZD programme will show if this is to be the case in the future as well. NOTES 1. Elementary school in Croatia has eight grades, starting at ages six or seven through to 14 or 15. Elementary school is obligatory. At the age of 14 or 15 pupils enrol into secondary school, where they might stay for three or four years. Some students enrol into craft or technical schools, which offer threeor four-year courses. On completion of secondary school students might go on to university. 2. The Croatian newspaper Feral Tribune recently reported on pupils who feel pressurized into attending Catholic instruction. The paper considers this to be a growing phenomenon (Lasic ´, 2007: 17). 3. According to Article 140 of the Croatian constitution, international agreements are an integral part of Croatia's legal system and take precedence over national law (Škrabalo and Juric ´, 2005: 179). 4. In the curricula of Catholic instruction for elementary schools, 17 school hours in total are dedicated to human sexuality in the last three grades (pupils aged 12-14 years) (Hodz ˇic ´, 2003: 14). 5. The experimental GROZD health education programme comprises five modules, one being human sexuality, which teaches about sex. 6. 'Three-year secondary school' refers to the craft and technical schools that some secondary students attend (see note 1).

European Journal of Women's Studies 15(4)


Farideh Heyat London

And Baku

New Veiling in Azerbaijan Gender and Globalized Islam

Keywords:

In the past few years, the growing presence of veiled women in Azerbaijan, particularly in the capital city, Baku, has been striking. This article traces the background to Islamism in Azerbaijan under the state dogma of atheism, and the post-Soviet changes that have facilitated a resurgence of religion in the country. It examines the motivations and the generational divide among women who have recently adopted veiling. Notions of 'traditional' and 'modern' are questioned here, pointing out the impact of identity politics and foreign Islamic forces on Azerbaijani society in today's increasingly globalized world. Furthermore, the article reveals the tensions and insecurities in the independent era that have reinforced the rise of Islamic ideology in the country and the contradictions involved in new veiling for Azeri women.

One of the striking social changes of the past few years in Azerbaijan is the increase in religious following, and the growing presence of veiled women on the streets of Baku. On the surface, this indicates a return to tradition and resurgence of Islamic belief and practices, in line with the increasing global popularity of Islam. However, a closer examination reveals many facets of the phenomenon in Azerbaijan that are at odds with its 20th-century history of social development. Following the breakdown of the Soviet system, the country emerged from 70 years of atheistic rule and various stages of modernization under a Communist regime that brought mass employment, compulsory primary and secondary education, and equality in law for women. More crucially, the unveiling of women, a process that took a few decades to fully accomplish and entailed great sacrifices by some of its pioneers in the 1920s, was embedded in the collective psyche as a major achievement by the Soviet regime. mourning ceremonies (yas) [START_REF] Lemercier-Quelquejey | Islam and Identity in Azerbaijan[END_REF]. Furthermore, under the Soviet system, with atheism as the official doctrine, the state denied access to religious knowledge, which led to a loss of religiousness (retaining religious knowledge) among the great majority of people. But ironically, religiosity (using religion as an idiom, manifested in frequent references to Allah and retaining strong religious sentiments) flourished. This process of privatization of religion, driving it from the public arena to the private realm of the home and kin group, and its consequent impact on gender relations and expectations of womanhood have been discussed for the Azerbaijanis [START_REF] Heyat | Azeri Women in Transition: Women in Soviet and Post-Soviet Azerbaijan[END_REF][START_REF] Tohidi | Soviet in Public, Azeri in Private: Gender, Islam and Nationality in Soviet and Post-Soviet Azerbaijan[END_REF][START_REF] Tohidi | The Intersection of Gender, Ethnicity and Islam in Soviet and Post-Soviet Azerbaijan[END_REF] and for the Tajiks [START_REF] Harris | Control and Subversion: Gender Relations in Tajikistan[END_REF][START_REF] Tett | Guardians of Faith: Women in Soviet Tajikistan[END_REF]. In my book on Azeri women [START_REF] Heyat | Azeri Women in Transition: Women in Soviet and Post-Soviet Azerbaijan[END_REF], I have discussed the dualistic system of education that evolved in the early years of the Soviet regime in Azerbaijan, leading to a dichotomous approach to religion by the individual; a case of 'religious hearts and atheist minds' (Heyat, 2002: 140). Coming from a strong religious tradition, Azeri children in the 1920s and 1930s were receiving atheist education at school, while at home they were brought up by parents and grandparents who observed Islamic mores and performed their religious duties. Many women of mid-generation today (those over 50) still remember their grandmothers wearing the large headscarves, kalaghe, performing their daily prayers, namaz, fasting and attending the religious rituals of marsiyeh. 4 Along with religious practice in the home, a basic belief in God and many religious concepts and mores were inculcated in the children of that first generation. However, in the decades that followed the ban on religion, with the imposition of atheism and the growing interethnic mix (socializing with Russians, Armenians and Georgians), many of the religious prescriptions and norms, such as those regarding dietary prohibitions and gender relations, were weakened or eroded. Nevertheless, a basic belief in God, or more precisely, the fear of Allah, remained in the hearts and minds of the population. As a result, throughout the Soviet period certain religious practices such as visiting shrines, ziyarat, paying alms, nazir, and religious tax, fitre (paid at the end of Ramadan) remained strong, even if the wording of namaz were forgotten and nobody fasted any longer. The isolation of the Azerbaijani religious establishment from its Shi'a sources of authority (in Iran and Iraq) also led to a confusion of religious belief and folk practice. Consequently, as in Central Asia, religion and ethnicity formed complex and interchangeable frames of reference to which cultural norms and practices were ascribed in a fluid way (Gross, 1992). Thus, being a Muslim and an Azerbaijani became synonymous, attributing many ethnic customs and cultural norms, including aspects of gender relations and femininity, to being Muslim, Musulmanchilik [START_REF] Dragadze | Islam in Azerbaijan: The Position of Women[END_REF]. Islam thus encompassed an identity category far beyond religious belief and labelling.

When the country gained its independence in 1991, it was against this backdrop of ideological confusion and ignorance of religious knowledge that the doors opened onto the outside world and increasing contact began with the surrounding Muslim countries. Saudi Arabia and the Gulf states, with their huge resources and Islamizing agenda, Iran, with its desire to promote political Islam and Shi'ism, and Turkey, with its growing Islamism, all entered the scene. Thus in the 1990s an increasing number of mosques and madrasahs were built and renovation of shrines and old mosques took place. With the support of Saudi, Iranian and Iraqi governments, pilgrimage trips to Mecca, and the holy Shi'ite sites in Iran (Mashad) and Iraq were also facilitated.

The reaction of the Azerbaijani government to the influx of Islamist groups and foreign religious organizations and charities, and their publications, was to initially adopt a completely open door policy. The political turmoil in the country, war with Armenia and the resultant refugee situation were the major problems for the state. In the post-Soviet ideological vacuum, identity politics in Azerbaijan, as in the other formerly Soviet Muslim republics, promoted Islamic beliefs and practices. Christian churches and missionary groups, as well as other denominations, also began to proselytize, often through charitable activities.

But by the end of the 1990s, restrictions were introduced to curb the activities of religious groups, requiring them to register officially. Two official bodies took charge of their monitoring: the State Committee for Religious Affairs and the Caucasus Muslim Board. The latter was headed by the chief imam of the Taza Pir, the largest old mosque in Baku. However, of the estimated 2000 different religious groups currently in operation, only 347 have received registration. Those most under pressure are the fringe groups not traditionally known in Azerbaijan, and the more radical Muslim mosques. These include the Baptists, Jehovah's Witnesses, Hare Krishna and Wahhabi Muslim groups. Successive governments have had a particularly difficult task to balance: on the one hand, the post-Soviet craving for religious knowledge and spiritual fulfilment; on the other, the fear that a militant Islamist group might become a source of opposition, with the power to mobilize large numbers of people.

There was a warning of the latter in the disturbances in 2002, following the government's imposition of control over religious activity in the small town of Nardaran, neighbouring Baku, in which one person was killed and many injured. 5 The harassment of the congregation of the historic Juma mosque in Baku's Old Town, whose imam had voiced political ambitions, and his removal, was another indication of the state's attempts to quash discontent voiced by the fledgling autonomous Muslim establishment in Azerbaijan. However, political Islam has not as yet made any significant inroads in the country. In the southern region, bordering Iran, the Iranian attempts to radicalize the local population in the 1990s were met by stiff resistance from the local clergy and the authorities. Similarly, much of the activities of the Wahhabi Islamist groups in the north of the country, where the majority are Sunnis, were obstructed. 6 The term 'Islamist' is often used indiscriminately in the West to refer to religiously inspired political movements across the world who differ vastly in their outlook on issues of democracy, human rights (including women's rights), the state and nationalism. Olivier [START_REF] Roy | The Failure of Political Islam[END_REF], in his major study of radical Islamism, points to its common call to fundamentalism, while at the same time, paradoxically, its attempts to integrate modernity. Radical Islamists today, he argues (Roy, 1994: 79), attempt to re-Islamize society at a grassroots level, with the aim of conquering it through reform of mores centred on the return to individual religious practice that will promote public virtue and maintain personal piety. This line of thinking is very much evident among the Wahhabis/Salafists in Azerbaijan, a Sunni sect rapidly growing among the educated young in Baku. They adhere to the ideology of Salafiyya (return to ancestors), a 19th-century Muslim fundamentalist movement inspired by Muhammad ibn Abdal-Wahhab. Their main centre is the Abu Bakr mosque in Baku, established in 1998 with Kuwaiti funding and led by a charismatic young Azeri imam, Gambet Suleymanov. He was educated in Medina in the 1990s, and is highly respected by his congregation for his intelligence and his integrity. Today, this mosque attracts the largest congregation, with its Friday prayers being attended by up to 10,000 men. [START_REF] Duval | New Veils and New Voices: Islamist Women's Groups in Egypt[END_REF] points out that Salafi followers, prominent in Egypt, have synthesized actionoriented Islamism with Sufism. They strive for social change through self-discipline in purifying oneself from previous sins, which would then reflect on the outside, and the whole society.

Similarly, Suleymanov preaches the need for individuals to start with cleansing and purifying their inner self and gaining piety before they can effect social change and deal with inequalities. They can then work on their families, neighbours and friends. He states that the great attraction of religion today is the inner peace and stability it offers. 'The youth especially, are confused by all the changes and the social upheavals, globalization, the problems with Karabakh [conflict with Armenia], and the growing wealth gap. They feel disturbed and they are looking for ways to calm their anxieties.' 7 Suleymanov offers a rationalist view of religion distinct from traditional beliefs and practices (such as veneration of saints and shrines and payment of alms in fulfilment of wishes) that is particularly appealing to his educated and professional followers. In contrast, the leadership of the main mosque in Baku, Taza Pir, are perceived as being only interested in enriching themselves through religious donations and commercial deals. For the young, educated women in Azerbaijan impressed by the messages of Islamist movements, veiling is a public expression of their new identity as socially responsible, pious individuals.

NEW VEILING: INDIVIDUAL INITIATIVES AND POLITICAL CHALLENGES

Studies of the new veiling phenomenon among various Muslim communities [START_REF] Duval | New Veils and New Voices: Islamist Women's Groups in Egypt[END_REF][START_REF] Hessini | Wearing the Hijab in Contemporary Morocco: Choice and Identity[END_REF][START_REF] Jansen | Contested Identities: Women and Religion in Algeria and Jordan[END_REF][START_REF] Guindi | Veil: Modesty, Privacy, and Resistance[END_REF][START_REF] Watson | Women and the Veil: Personal Responses to Global Process[END_REF][START_REF] Yegenoglu | Colonial Fantasies: Towards a Feminist Reading of Orientalism[END_REF] point to a number of common features. Most notably, this is no return to old traditions of veiling and confinement of women to the home environment, but a voluntary act of self-assertion in adopting a form of dress that signals respectability (through an image of modesty and chastity) while leading an active public life. In the case studies presented, the women often refer to the greater degree of mobility in the public space and freedom from male harassment they have enjoyed since adopting Islamic dress. [START_REF] Hessini | Wearing the Hijab in Contemporary Morocco: Choice and Identity[END_REF], in her analysis of women wearing the hijab in Morocco, points out the importance of division of space in Muslim communities and assumptions about differences between men and women that underline the respect for veiled women among them. In effect, a veiled woman in the public space is presumed to signal distance and unavailability to unrelated males, thus warding off any unwanted approaches. This aspect was also pointed out by my young informants who found being veiled helpful in gaining permission from jealous husbands and possessive parents to move more freely outside the home.

Ask and Tjomsland point out that today's Islamic dress, far from being traditional, 'reflects innovation made by the younger generation of women who use change of clothing to accentuate their identity and response to a changing world, and thereby even create a resourceful place for themselves within that world' (Ask and Tjomsland, 1998: 11). Indeed, the changes in form and meaning associated with the veil, and more broadly women's attire, in the 20th-century Middle East affirm its political nature and its relation to identity politics of the region. The most notable example here is perhaps the case of Iran where the traditional veil, chador, was outmoded in the process of modernization under the Shah. Then, by the end of his regime in 1979, a new modified form of veiling was adopted by the revolutionary women protesting against his regime and western imperialism in Iran [START_REF] Azari | Women of Iran: Conflict with Fundamentalist Islam[END_REF]. In recent years, the tide has turned once more; women are in the forefront of resistance to the theocratic regime, dressing in ways that are often considered un-Islamic, badhijab. 8 The ironies of the situation in Iran are not lost to Azerbaijanis, whose country lies just across the border. In my recent discussions with various groups of self-employed women in Baku (street vendors, beauticians, tailors), they often remarked with surprise and irony that while so many Iranian women tourists cannot wait to cast off their headscarves the moment they arrive, some Azeri women are today voluntarily putting it on. This was an issue that members of the largest women's NGO in Azerbaijan, Women's Rights Defence Committee, were particularly concerned about. The head of the group, Novella Jafarova, who has been campaigning for democracy and women's rights in Azerbaijan since independence, voiced the group's concerns in an interview, as follows:

Ten years ago we really didn't think religion and Islam were an issue or a problem for our country. But today as we see all these recently veiled women we begin to fear a fate such as that of women in Iran. We certainly cannot afford to lose any of our gains from the Soviet era. But if we are not careful, Islamism could creep up on us and we'll all be pushed back under the chador.

The association between veiling and infringement of women's rights has not so far surfaced much in the public discourse in Azerbaijan, and was not acknowledged by any of my veiled informants. As becomes clear later in this analysis, equality under current laws (a legacy of the Soviet system) is taken for granted and restrictions for women under the Sharia law are dismissed as irrelevant by these women.

SHADES OF HIJAB: AZERI FEMININITY UNDER COVER

In Baku today there are a multitude of Islamic stores selling outfits for women observing the hijab, as well as CDs and cassette tapes containing religious lessons, sermons and Koranic readings. The long skirts, tunics and headscarves on display are often as colourful and pretty in design as the clothing sold in nearby fashion boutiques. The local understanding of being veiled is to be covered head to foot, except for the face and hands, though a great variety of styles are adopted, from a long, loose coat-type dress to tight jeans and tops. The current notions of Islamic femininity, requiring modesty, chaste demeanour and way of dress, were in fact highly idealized feminine traits in Soviet Azerbaijan (Heyat, 2002: 194;[START_REF] Tohidi | Soviet in Public, Azeri in Private: Gender, Islam and Nationality in Soviet and Post-Soviet Azerbaijan[END_REF]. Even as late as 1992 (during my first visit to Azerbaijan), it was extremely rare to see women in trousers or short skirts on the streets of Baku. Furthermore, the ethnic Azeri culture under the Soviet system, as with many other male-biased patriarchal cultures, assumed women's primary responsibility to be the domestic care, and men's, the financial maintenance of the home. The present-day rise in religiosity and intrusion of Islamist ideology into family life, therefore, does not create conflict or tension in many aspects of everyday life. The traditional separation of male and female space is still observed today, for example in the case of mourning ceremonies (yas), or weddings (toy) in rural areas, and restaurants and cafes in provincial towns being a male domain.

Since the 1990s, with the oil boom, the presence of foreign companies and NGOs and travel abroad, much of the social scene in Baku has changed dramatically [START_REF] Heyat | Globalisation and Changing Gender Norms in Azerbaijan[END_REF]. Western cultural influences are paramount everywhere, beamed through the media (satellite, Turkish and Russian TV channels), wide use of internet and student exchanges abroad. Most young Azerbaijanis are indeed socially and culturally oriented towards Europe and the US. Today, there are growing employment opportunities for educated young women with a knowledge of western languages, and greater autonomy for those with absent fathers and husbands (mostly due to massive labour migration to Russia and elsewhere). Young women appearing on their own, often dressed in revealing western fashion, is a common sight, and considered sexually provocative to recent male migrants from rural regions. Some of these are refugees and displaced persons in the war with Armenia, others have come in search of employment and to escape poverty in the regions. The social upheavals of the past 15 years, the prominence of money as the new arbiter of social life, the astronomical rise in corruption and the display of permissiveness in the media, have all led to a sense of insecurity and loss of morality in society, for which some men and women consider religion as a panacea. [START_REF] Gureyeva | Veiled Women in Azerbaijan: Gender, Islam, and Modernity[END_REF], in her study of new veiling among women in Azerbaijan, confirms this. All her respondents had pointed out that Islam and veiling had empowered them by giving them a sense of stability and strength, and helped them gain confidence in themselves and in their future. The accounts of my key informants that follow elucidate similar points, while revealing the contradictions in their status as independent women, and the gender norms they were subject to requiring them to submit to male authority.

Laleh is a 19-year-old, third-year student of international relations at Baku State University. Her only sibling, a younger sister still at school, has not followed her example of veiling. Laleh presented herself to me as a Sunni Muslim and a Salafi, arguing that Sunnism was 'true' Islam. Shi'ism, the sect her family believed in, was a later invention, she said, 'a deviation from the original path'. Her parents are both university-educated professionals. According to Laleh, around 20 percent of the students at her university are newly veiled. She, herself, had become interested in religion during her last years at school when Islamic following was becoming popular among her fellow pupils. Her family, however, displayed no interest in religion and when she decided to veil, her parents, particularly her mother, were at first against it. It took many arguments to convince them that she was making the right choice. Her grandfather had been especially baffled to see her covered up. His generation had struggled hard to cast off the veil. He had commented to her: 'You look like your great grandmother, why do you want to turn the clock back?' The establishment in Azerbaijan are generally unsympathetic to the idea of veiling and suspicious of veiled women. Such women are subject to discrimination in employment and have difficulty in obtaining passports and identity cards (photographs of veiled women are rejected).

In 2006, Laleh finally made up her mind to embark on veiling. She then went with a former class mate to the main mosque near her home, the Abu Bakr mosque in central Baku, and took her vows of repentance, toabeh. Since then she has been attending the mosque at least once a week, taking religious lessons and attending lectures by the imam. She also regularly visits Islamic websites that publish religious news and views in Azeri and Russian language. She does her daily prayers, namaz, five times a day in the Sunni tradition. 'I am very happy now that I have made my decision', Laleh told me when we first discussed her recent religiosity. 'I feel pure and virtuous, and I get a lot of respect from men on the street. On the bus and the metro, even older men get up and offer me their seat.' Laleh's cousin, 23-year-old Yasmin, was another recent born-again Muslim who attended the Abu Bakr mosque. She had been very inspired by Laleh's study of Islam and religious devotion. She believed her to have become more confident and articulate since then. Yasmin was married, with a two-year-old son. She lived with her in-laws who were not religious and questioned her recent adoption of the veil. She had married her husband at the end of her first year of university. He had turned out to be very possessive and jealous of her outside movements. She had dropped out of studying after her first year and had a baby. Now, since being veiled, he seems more relaxed about it, so she has embarked on a new course of study. He himself took up religious observance over the past couple of years but found it difficult to keep up with. Yasmin's brother, on the other hand, is steadfast in observing his religious duties since his toabeh three years ago, though he did not pressure her to wear the veil. But now Yasmin and her brother are both encouraging their mother to take up religion. They have often discussed with her the sinful ways in which many people in Azerbaijan, especially the wealthy, live their lives, and warned her of ghiyamet (Judgement Day) and the need to follow Allah's commands.

The fear of Allah and ghiyamet was also articulated by a number of my other informants, such as Nigar, a 24-year-old doctor, who graduated a year ago. She is married with no children, and is currently unemployed. To get a job at a hospital she would need to pay a substantial bribe to the chief consultant who then passes part of it to higher up authorities. 9 Nigar's family are all professional people, but not rich. She began praying regularly and keeping fast four years ago. She would like to veil but is wary of her mother and mother-in-law's disapproval. She is also concerned that it may prejudice her job opportunities. Her former class mate, Gulnur, took up the veil a year ago, and has been a major influence on her. But then she already had a job as a dentist at her brother's private clinic. Nigar's husband, a graphic designer, has very recently started doing the namaz, persuaded by her. He attends the Abu Bakr mosque for Friday prayers, along with Gulnur's brothers.

Nigar estimated that around 15-20 percent of the female students at her former university are veiled. She thinks that influences from Turkey are partly responsible; students from provincial Turkey with a religious outlook and the Turkish religious TV channel are promoting Islamic ideology in Azerbaijan. The religious channel regularly broadcasts documentarystyle programmes on the topic of miracles in the Muslim world and popular serials that depict salvation through religious faith. Nigar seemed particularly burdened with the notion of sin, gunah, and the struggle to absolve oneself from it. Today in Azerbaijan, she told me, there are too many people who don't care about the welfare of others and only think about their own pockets and their families; the fear of Allah is missing among them. When she discovered that I did not practise Islam, the religion I was born into, she kept asking me: 'but aren't you afraid of ghiyamet?' She went on to tell me that she had felt lighter and happier as a person since she started performing the namaz regularly.

Nigar's deep-rooted fear of Allah was part of the belief system that had never been eroded from the hearts and minds of Azerbaijani Muslims living under the veneer of atheism. The strength of this feeling was also reflected in the survey of religious following among the youth (mentioned earlier) in which 80 percent of the respondents had a strong belief in God, and only 2 percent professed to be atheist.

For Azeri youth today, subject to the global rise of Islam and proliferation of Islamist movements, the atheism of the Soviet era is associated with their parents' generation. Paradoxically, today's greater mobility and the intrusion of western youth culture encouraging autonomy and individuality may be the driving forces behind the rebellion by those young educated women who adopt the veil against their parents' wishes. For the middle-generation Azeri women, however, some of whom have also adopted new veiling as part of their strict observance of Islam, the motivation may be in their need to find solace at times of crisis in life and to face the challenges of the post-Soviet era of economic and social insecurities. This became clear in a focus group discussion I held with members of a religiously devout group, the Al Zahra Women's Association. A selffunded, independent organization with 2500 members, mostly university educated, it was registered as a religious charity in 1998. The founder of the group, a former member of the Azerbaijan Women's Association (AWA; successor to the old Zhensoviet) is in her fifties, and from an old religious family. I have known her well since my involvement with the AWA in 1994-5. Following a number of trips to Iran in the early and mid-1990s, she decided to take up veiling in 1998.

At my meeting with some of the core members of the Al Zahra group, there were nine women present, all of them veiled. They ranged in age from mid-forties to late fifties, all professional women who were either in early retirement, or unemployed. 10 Among them there were a number of teachers, accountants, administrators, a chemist and a painter. Their accounts of what had inspired their new found religiosity revealed the passage of a particularly difficult time in their life, such as bereavement or serious ill health, just prior to their conversion. The most dramatic case was that of an Azeri-Russian former teacher who had joined the group following the murder of her 18-year-old daughter. The feelings of love and reassurance she had received from reading the Koran and from the group members had helped her survive the tragedy.

For most of the women in the group, I was told, the pilgrimage to Mecca, or Mashad, had been the defining moment in their new religious zeal and observance of the hijab. All the women spoke of muhabbat (love) as their great gain in their new way of life. Some of the women began to cry as they spoke of their recent spiritual enlightenment. They were also very keen to speak of the bond they had formed as members of their group, helping and supporting each other, emotionally, as well as materially. 'We are closer than sisters', a number of them stressed to me. For these women, as for those in the case of Kyrgyzstan I have discussed elsewhere [START_REF] Heyat | Re-Islamisation in Kyrgyzstan: Gender, New Poverty, and the Moral Dimension[END_REF], the sense of shared problems and connectedness in the face of post-Soviet upheavals seemed to be a source of empowerment, confirming their allegiance to the ideology of the group and its requisite practices.

On the question of women's rights under Islam, however, the group did not seem very willing to engage in debate. When I mentioned the issue of polygamy, two of the women simply stated that they would seek a divorce if they found out that their husband was engaging in a serious relationship with another woman. One of the women mentioned that in Azerbaijan a man cannot marry two women and after a divorce, custody of children is usually given to the mother. Another one claimed that according to the Koran a man has to obtain his wife's permission to marry a second wife. The founder of the group then began to talk about the complexities involved in Sharia law and that it was open to discussion and debate. 'We have our laws, the civil laws, and we don't want them changed. Sharia can only be applied in a truly Islamic state', was her final assessment, with which other women in the group seemed to concur.

Ignorance of discriminations in Sharia law was also common among the newly veiled young women I had discussions with. They seemed a little baffled and surprised when I pointed out some of the gross inequalities women would be subjected to under Sharia law. But they did not seem particularly concerned. When I asked Yasmin, for example, what would she do if her husband wanted to exercise his Islamic right to take a second wife, she simply said 'I would divorce him'. She seemed to take it for granted that under Azerbaijani law a woman had as much right as a man to petition for divorce on grounds of incompatibility, and she would automatically be awarded the custody of her young son. On the question of imposed male authority, however, this was an element of their ethnic/national culture that most Azeri women did not challenge vocally, but managed to accommodate their own wishes and demands despite it. The ambiguities and contradictions in Soviet Azeri culture with regard to femininity and gender relations had facilitated women's agency and offered a degree of empowerment while retaining male superiority in public discourse and in gender relations at a formal level (Heyat, 2002: 219). Women could do and did much, behind the scenes and in collaboration with their close kin and female friends, yet always deferred to their husband, father or older brother's authority [START_REF] Tohidi | Soviet in Public, Azeri in Private: Gender, Islam and Nationality in Soviet and Post-Soviet Azerbaijan[END_REF][START_REF] Tohidi | The Intersection of Gender, Ethnicity and Islam in Soviet and Post-Soviet Azerbaijan[END_REF]. For example, when I brought up the issue of male authority in Islam with Nigar, the young doctor, she told me quite bluntly: 'If I get ready to go out and just before leaving the house my husband says to me "Stay in the house, don't leave", I will obey him and not go out.' When I asked her what would be his response if she asked the same of him, she hesitated for a moment, then replied: 'He would do the same. We respect each other's wishes.' I remained sceptical, but felt that in her brief hesitation Nigar reflected the tension between the traditional Azeri gender norms, based on notions of male control and female submission, and her status as a western-oriented professional woman expecting full equality. The contradiction born of this schism, however, is very rarely articulated in public discourse in Azerbaijan. [START_REF] Harris | Control and Subversion: Gender Relations in Tajikistan[END_REF], in her analysis of gender identity and performance in Tajikistan (a society culturally similar to Azerbaijan), makes the argument for a 'variant gender performance' to explain women's intentional projection of an image of submission to male authority to conform to Tajik society's gender norms, and thus gain social approval. But she maintains that gender identities and performances are never fully internalized. They are only assumed to suit the circumstance, like the donning of a Greek mask (Harris, 2004: 21). This may be too positivistic an interpretation of women's behaviour, when in fact every individual in these formerly Soviet Muslim societies was subject to observing sets of dualities (official/unofficial, and inner/outer self) in their speech and behaviour. These were governed by strong rules of deference and social hierarchy emanating from their ethnic cultures, and the need for concealment in a secretive society. Today, one can see how in the light of the insincerities of the Soviet culture and the complexities born of the dualisms that governed their society, the young Azeris are attracted by the image of simplicity, honesty and purity projected through the religious groups' teachings, whether Christian or Muslim.

CONCLUSION

In Azerbaijan, the economic, social and political upheavals following the breakdown of the Soviet system have been unfolding in the era of globalization. As elsewhere in many Third World countries, a prominent feature of the latter has been the increasing wealth gap and inequality of access to western know-how and languages among social groups, and between centre and periphery [START_REF] Heyat | Globalisation and Changing Gender Norms in Azerbaijan[END_REF]. Baku has thus become a magnet for employment, business and educational opportunities in the country, attracting large numbers of rural migrants with more conservative social and cultural mores. It is also a place where there is greater prevalence of sexual permissiveness and a more acute contrast in wealth and poverty. Given the greater freedom of association in the city, it has offered fertile ground for foreign and emerging local Islamist groups to operate and publicize their message of salvation through personal piety. While a small minority of the Azeri population have turned to Christian churches and other denominations, the majority have reaffirmed their Muslim identity and taken interest in Islamic beliefs and practices, influenced by religious knowledge emanating from Iran, Turkey and the Arab states.

A visible and poignant consequence of the rise of Islam among Azeri women has been the adoption of the veil, in contrast to a long history of attempts at women's emancipation and unveiling under the Soviet regime. Their motivation for this may be diverse, ranging from peer pressure, to finding solace and support among fellow-believers, or simply due to ideological conviction. More often though, it is a combination of these. Nevertheless, globalizing influences that underline this relate to the phenomenon of new veiling in many Muslim countries around the world. The veil, in its modern, non-traditional form and usage has acquired symbolic meaning that signifies women as bearers of national identity and moral standards, expressing their protest against western consumerist culture. Furthermore, it has given individual women a degree of agency and empowered them in their public presence. In Azerbaijan, however, there is a more complex process at play.

During the 20th century, despite certain male-biased, patriarchal features of the ethnic Azeri culture, women gained societal acceptance of their public presence and equal rights in education, employment and under the law. The newly veiled women in Baku are not unaware of their present advantageous position, even if they take it all for granted. They do not want to turn the clock back. The phenomenon here has a generational dimension. The youth are more easily influenced by globalized Islamist movements targeting the young through the internet, television and the news media. For young women, distanced from the atheism and anti-veil outlook of their parents and grandparents' generations, the veil signifies rebellion against establishment and a protest at the rampant corruption and gross inequalities in their country. They are attracted by the messages of sincerity and honesty imbedded in the religious worldview, in contrast with the culture of concealment and the dualistic presentation of the self that dominated the lives of former generations.

What is problematic in all this is the fact that a notion of 'natural' difference between men and women underlines Islamic social order, and designates different roles for men and women. In this worldview, also publicized through Islamist publications and websites in Azerbaijan, female sexuality is deemed as dangerous and damaging to the social order, and the veil is considered an essential means of its suppression through the control of the female body and the imposition of strict moral codes on women. For Azeri women, the adoption of the veil, though initially and in some respect liberating, in the long run confirms their social submission to ethnic and religious norms that are inimical to their independence and empowerment. Although at present the state in Azerbaijan is strictly secular, the growth of Islamism and the deepening ideological divisions in the country, along the lines in Turkey, may endanger the secular foundation of the state. The challenge for Azeri women in future years will be to safeguard their gains of the past and build on these for a more equitable future. NOTES 1. This statue was erected in 1930 to commemorate the murder of an Azeri woman by her father outraged at her unveiling. It was a culmination of punishments, harassments and even murders of unveiled women in Baku in the late 1920s, in response to the unveiling campaign by the Communist Party (Heyat, 2002: 131). 2. These are government estimates provided by the Azerbaijan International Religious Freedom Report 2006, released by Bureau of Democracy, Human Rights, and Labor, US Department of State; at: www.today.az/news/society/ 30286.html 3. Among the practising respondents, two-thirds were Shi'a and one-third Sunni. The survey was carried out jointly by the Centre for Research on Religion, and Republican Youth Movement, found in the islam.az website, at: www.islam.az/az/modules/news/article.php?storyid=26 4. These take place during the holy month of Muharram, that peaks on the day of Ashura, commemorating the martyrdom of Imam Husain, the grandson of Prophet Muhammad, and also on the occasion of the martyrdom of his father, Imam Ali, the fourth Khalif after the Prophet. 5. A report of the clashes in Nardaran, traditionally one of the most religious villages around Baku, can be found at: religion.rus.ru/event/20020625html 6. For a full discussion on the Islamic following in Azerbaijan see the report 'Islamic and Ethnic Identities: Emerging Tendencies in Azerbaijan'; at: www.osce.org/item/23087.html 7. The statements attributed to Gamet Suleymanov are taken from an interview I conducted with him at the Abu Bakr mosque in June 2007. 8. In the past few years, young women in large cities such as Tehran and Karaj are wearing minimal size scarves, body hugging tunics, well above the knee, mid-calf trousers and heavy makeup. The regime's intermittent campaigns of warnings, harassment and punishment have so far proved unsuccessful. 9. The system of corruption in Azerbaijan has become more widespread since the breakup of the Soviet Union. In the field of employment in the public sector, for example, to get a professional job, it is often the case that in the absence of strong personal connections, substantial bribes have to be paid to the chief of the organization concerned. 10. Asian Development Bank's 'Azerbaijan: Country Gender Assessment' report, December 2005, indicates a much lower level of economic activity among women (59.5 percent), compared to men (83.6 percent).

European Journal of Women's Studies 15(4)


Renke Maas
email: maas@uke.uni-hamburg.de

S49-Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA)

Keywords: asymmetric dimethylarginine (ADMA), cardiovascular disease, DDAH, drug therapy, nitric oxide synthase inhibitor

Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are found in various clinical settings, including renal failure, coronary heart disease, hypertension, diabetes and pre- eclampsia. In healthy people acute infusion of ADMA promotes vascular dysfunction, and in mice chronic infusion of ADMA promotes progression of atherosclerosis. Thus, ADMA may not only be a marker but also an active player in cardiovascular disease, which makes it a potential target for therapeutic interventions. This review provides a summary and critical discussion of the presently available data concern- ing the effects on plasma ADMA levels of cardiovascular drugs, hypoglycemic agents, hormone replacement therapy, antioxidants, and vitamin supplementation. We assess the evidence that the beneficial effects of drug therapies on vascular func- tion can be attributed to modification of ADMA levels. To develop more specific ADMA-lowering therapies, mechanisms leading to elevation of plasma ADMA con- centrations in cardiovascular disease need to be better understood. ADMA is formed endogenously by degradation of proteins containing arginine residues that have been methylated by S-adenosylmethionine-dependent methyltransferases (PRMTs). There are two major routes of elimination: renal excretion and enzymatic degradation by the dimethylarginine dimethylaminohydrolases (DDAH-1 and -2). Oxidative stress causing upregulation of PRMT expression and/or attenuation of DDAH activity has been suggested as a mechanism and possible drug target in clinical conditions associated with elevation of ADMA. As impairment of DDAH activity or capacity is associated with substantial increases in plasma ADMA concentrations, DDAH is likely to emerge as a prime target for specific therapeutic interventions.

Introduction

The L-arginine-nitric oxide pathway is involved in the regulation of diverse physiological functions includ- ing endothelium-dependent vasodilation, platelet aggregation, neurotransmission, immune defense and apoptosis.1 Accumulating evidence links asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), to human disease.2 2 Elevated plasma ADMA concentrations are found in various clinical settings ranging from renal failure and liver failure to atherosclerosis, hypertension, diabetes and pre-eclampsia.3-11 Moreover, in patients with cardiovascular disease, end-stage renal disease, or critical illness, elevated plasma ADMA concen- trations independently predict progression of athero- sclerosis, future vascular events and/or overall mortality. 12-15 Several lines of evidence suggest that ADMA, being a NOS inhibitor, may not only be a marker of disease but a player. In human volunteers, infusion of ADMA has been shown impair to endothelium-dependent vasodilation, increase systemic and renal vascular resistance, and decrease cardiac output.3>16-1g These data suggest that chronic elevation of ADMA may directly promote vascular disease, which makes ADMA a promising new drug target. Studying the effects of commonly used drugs on plasma ADMA levels may be a first step towards gaining some insights into the mechanisms leading to elevated plasma ADMA concentrations. As ADMA may be both a marker and a player in cardiovascular disease it may therefore be difficult to discern indirect drug effects on ADMA levels related to improvement of the underlying condition from direct drug effects (such as drug-induced augmentation of dimethylarginine dimethylaminohydrolase (DDAH) activity).

It is the purpose of this review to evaluate possible mechanisms leading to the elevation of ADMA plasma concentration and critically to review first in vitro and in vivo data concerning potential ADMA- lowering therapies.

Formation and elimination of ADMA: mechanisms and targets for therapeutic interventions Asymmetric dimethylation of L-arginine residues in proteins The initial step in the endogenous formation of ADMA (Figure 1) is the asymmetric dimethylation of L-arginine residues of various cellular proteins Figure 1 Formation and elimination of ADMA: (1) S- adenosylmethionine is required as a source of methyl groups; (2) asymmetric methylation of L-arginine residues in proteins by type I protein-arginine methyltransferases (PRMTs); (3) proteolysis leads to liberation of ADMA; [START_REF] Tsikas | Elevated plasma and urine levels of ADMA and 15(S)-8iso-PGF2alpha in end-stage liver disease[END_REF] degradation of ADMA by dimethylarginine dimethlyaminohydrolase (DDAH); (5) carrier-mediated excretion of ADMA; (6) carrier-mediated uptake of ADMA; (7) renal filtration of ADMA; (8) carrier-mediated secretion and re-uptake of ADMA. by specific protein L-arginine methyltransferases (PRMTs).19,20 Type 1 PRMTs are considered the predominant enzymes responsible for asymmetrical dimethylation, 20 and S-adenosylmethionine (SAM) derived from L-methionine appears to be the principal methyl group donor for this reaction.21 Moreover, elevation of SAM promotes PRMT activity and sub- sequent formation of ADMA. The product of this methylation reaction, S-adenosylhomocysteine (which inhibits PRMT activity) is hydrolysed to L-homocys- teine, which, in turn, can be remethylated by methion- ine synthase to L-methionine.22 This reaction, which closes the methylation cycle, depends on vitamin BI2 and 5-methyltetrahydrofolic acid as methyl group donors. In principle, each step of this methylationremethylation cycle constitutes a potential target for therapeutic approaches to lower SAM levels and thus reduce substrate availability for asymmetric dimethy- lation of L-arginine residues.

Practical and clinical considerations, however, make formation of SAM and PRMTs unlikely targets. First, post-translational methylation of L-arginine residues is considered a universal biological process affecting hundreds of proteins, In most cases the effects of this methylation are still unknown. Thus, interference with this mechanism may have unforseen consequences.

Secondly, based upon their role in the homocysteinemethionine cycle, one would expect folate and vitamin B ~ supplementation to increase synthesis of SAM and subsequent ADMA formation. However, it was shown in patients with increased plasma homocys- teine levels that folate lowered elevated plasma ADMA concentrations.23 In this study, which unfor- tunately lacked a placebo group, the beneficial effect of folate on ADMA levels was attributed to the reduction of homocysteine by folate. In contrast, in another study, supplementation with folate and B vitamins had no impact on ADMA levels.2a Proteolysis and formation of ADMA . When proteins are degraded, asymmetrically dimethy- lated L-arginine residues are released as ADMA. Considering the wide variety of asymmetrically dimethylated proteins it is very unlikely that suffi- ciently specific inhibitors of the proteasome involved in degrading these proteins can be found. Moreover, specific or nonspecific inhibition of protein degrada- tion could lead to accumulation of these proteins or peptide fragments, which potentially could cause a form of storage disease. Hence, proteolysis is unlikely to present a suitable drug target for reducing ADMA levels.

Specific metabolism of ADMA by DDAH ADMA is selectively degraded by DDAH to citrulline and dimethylamine.25 In humans there are two major isoforms of DDAH (DDAH-1 and DDAH-2) with partly overlapping tissue distributions26 in kidney, liver and small intestine (Table 1). Presently, it is not known what percentage of the endogenously formed ADMA is directly metabolized in the cells where it is formed and how much is released from the cells into other tissues to be metabolized or excreted. It is also not known which DDAH isoform or which organ dominates ADMA degradation in humans in vivo. Rising plasma concentrations in renal3 or liver failure4 strongly suggest, however, that at least some tissues release a substantial fraction of the endogenously formed ADMA to be metabolized or excreted elsewhere. With an estimated 'organ weight' similar to that of the liver, the endothelium could be another major site of ADMA metabolism (Table 1).27 Current estimates of the relative expression of the two iso- forms are mainly based on mRNA data. DDAH-1 I expression tends to dominate in tissues with a high expression of the neuronal isoform of NOS (nNOS), whereas DDAH-2 expression seems to follow the expression pattern of endothelial NOS isoform (eNOS). Analysis of the DDAH-2 gene and its promotor regions revealed potential binding sites for regulators of transcription (STAT, PPAR/RXR, NF-KB and IRF-1) as well as features consistent with the function of a housekeeping gene (absence of canonical TATA boxes and a CpG island around the transcription start sites). Specific activators of DDAH expression are not yet known, but activation of DDAH expression is of course an interesting drug target.

In cell culture all-trans-retinoic acid increased DDAH-2 expression.28 Regulation of DDAH-1 expression is even less well understood. In smooth muscle cells interleukin-1 beta upregulates DDAH-1 I expression at the protein level.29 DDAH contains four highly redox sensitive cysteine groups, which appear to be crucial for its catalytic function.25,30 DDAH activity may also be regulated by S-nitrosylation of a reactive cysteine residue (Cys-249),3° providing some form of an indirect negative feedback, especially for inducible NOS (iNOS)-derived nitric oxide (NO).

Therapeutic augmentation of DDAH expression or activity: a word of caution Although increased NO synthesis due to upregulation of DDAH expression or activity is usually desired in cardiovascular disease, it may have catastrophic effects when occurring in tumors (by promoting NO- mediated angiogenesis). Indeed, recent studies suggest that DDAH activity is increased in human tumors. [START_REF] Kostourou | Effects of overexpression of dimethylarginine dimethylaminohydrolase on tumor angiogenesis assessed by susceptibility magnetic resonance imaging[END_REF] Moreover, overexpression of DDAH-1 or -2 enhances tumor growth and tumor angiogenesis.32

Transport and exchange of ADMA When assessing drug effects on ADMA levels, a major drawback of all available clinical data has to be con- sidered. We currently measure the plasma concentra- tion, which may represent only some form of 'cellular spillover'. Little is known regarding the correlation of plasma ADMA and intracellular ADMA concentra- tions in vivo. Thus, even a normal or normalized plasma ADMA concentration may not completely exclude severe derangement of intracellular ADMA concentrations by disease or drugs.

Given its structural similarities to L-arginine, the cationic amino acid ADMA most likely shares carrier systems with L-arginine to leave or enter cells.33 Indeed, early in vitro data suggest that transport of ADMA may at least in part be mediated by y+ carri- ers.34 Clinical data regarding the precise transport mechanisms for ADMA and their regulation in vivo are not currently available.

-Renal filtration and excretion of ADMA Elevated plasma levels of ADMA were first reported in patients with chronic renal failure by Vallance and co-workers. 3 We now know that the combination of renal filtration, tubular secretion, tubular reabsorption and degradation by renal DDAH result in a net renal extraction of about 16% of circulating ADMA. 35 Presently it is difficult, however, to estimate the rela- tive contribution of each mechanism. It is interesting that symmetric dimethylarginine, which is chemically very similar to ADMA but not metabolized by DDAH, has a renal extraction rate of only 10%. This differ- ence may be interpreted as evidence for a substantial contribution of renal DDAH activity to the renal extraction of ADMA.

Exogenous sources of ADMA Protein-L-arginine methylation is a universal biological principle found in bacteria as well as in plants and animals.36 It is therefore very likely that free and protein-incorporated ADMA37 is also taken in with the diet, modulated by dietary components, or formed by resident colonic bacteria. This offers several further targets for ADMA-lowering therapies that have not yet been investigated.

Major disease mechanisms leading to elevation of ADMA in human disease

Shear stress

In vitro, shear stress may have divergent effects on ADMA.38 Moderate shear stress was found to upregu- late PRMT expression while DDAH activity was unchanged, resulting in enhanced cellular ADMA release. In contrast, when cells were exposed to a higher shear stress, PRMTI and DDAH activity both increased, resulting in normalization of ADMA levels.

High blood glucose and impaired glucose ' . tolerance Elevation of plasma ADMA levels have been observed in a rat model of diabetes, and DDAH activity was found to be significantly impaired in human cells exposed to high concentrations of glucose.39 Since it was shown that impairment of DDAH activity could be alleviated by polyethylene glycol-conjugated superoxide dismutase, impairment of DDAH activity by glucose-induced oxidative stress was suggested as the major underlying mechanism. In humans the situation appears to be more complex. In volunteers without dia- betes, plasma ADMA levels were found to be correlated with individual insulin sensitivity but not with blood glucose level.10 Clinical data concerning plasma ADMA levels in patients with diabetes are somewhat conflicting: some studies have shown an elevation of ADMA4° while others demonstrated a reduction. 41 Oxidative stress Several independent lines of evidence indicate that impairment of DDAH activity by oxidative stress is the final mechanism leading to elevation of ADMA in diverse clinical conditions.42 DDAH contains four highly redox sensitive cysteine groups, which appear to be crucial for its catalytic function. [START_REF] Ogawa | Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase, from rat kidney[END_REF][START_REF] Leiper | S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase[END_REF] Oxidized low-density lipoprotein (oxLDL) but not native LDL was found to decrease DDAH activity43 and increase cellular ADMA liberation. In cell culture, oxLDL and high concentrations of native LDL lead to upregulation of PRMTs and cellular ADMA synthesis that could be prevented by antioxidants [START_REF] BöGer | LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethioninedependent methyltransferases[END_REF] Unfortunately, impairment of DDAH activity by oxidative stress or upregulation of PRMTs may not be easy to overcome in humans. A Finnish study found no association between plasma ADMA levels and dietary vitamin E or C intake. [START_REF] P&auml | Dietary composition as a determinant of plasma asymmetric dimethylarginine in subjects with mild hypercholesterolemia[END_REF] In an open label study, 800 IU vitamin E over 6 weeks had no significant effect on plasma ADMA. [START_REF] Saran | Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study[END_REF] Moreover, in a very recent clinical trial N-acetyl-cysteine had no effect on plasma ADMA levels. 47 Hyperhomocysteinemia In animals48 and humans49,so experimental hyperho- mocysteinemia is associated with elevation of plasma ADMA. Two (not necessarily exclusive) mechanisms have been proposed to explain this finding: 1. Homocysteine may be remethylated to form L- methionine, which, in turn, serves as a methyl group donator for the methylation of L-arginine.22

Increased ADMA release by endothelial cells under high concentrations of methionine or homo- cysteine was reduced by the methylation inhibitor S-adenosylmethionine.44 In monkeys, dietary supplementation with B vitamins normalized homo- cysteine but did not alter ADMA levels or improve endothelial function 48 2. Homocysteine may also directly interact with the sulfhydryl groups of DDAH. In an in vitro bind- ing assay, biotinylated homocysteine was found to bind directly to This binding could be prevented by an antioxidant.

Drug therapy and ADMA: early clinical data

Statin therapy

Statins are among the most effective drugs for lower- ing cardiovascular risk associated with elevation of LDL cholesterol. Several lines of evidence suggest that the beneficial effects of statins are at least in part mediated by LDL-independent (pleiotropic) mecha- nisms such as improvement of endothelial function by increasing the bioavailability of NO. In animal exper- iments as well as in patients a high LDL cholesterol level was found to be associated with elevated plasma ADMA concentrations .48.52 Even though this finding does not seem to be found consistently in all patient populations,53 several investigators have tested the hypothesis that statin treatment may improve vascular function by reducing plasma ADMA (Table 2). In the majority of studies, statin treatment had no impact on plasma ADMA levels. 54-56 This would clearly argue against a direct connection between ADMA and LDL cholesterol in humans. Only rosuvastatin was shown to lower ADMAS~ but, given the negative results for the other statins, this finding remains to be replicated in other populations. Irrespective of the potential effects of statins on ADMA, recent studies suggest that ADMA may mod- ulate the effect of statins on vascular function.58 ~ ..... r

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers

In various conditions such as hypertension, diabetes and coronary artery disease, angiotensin converting plasma ADMA levels in these patient groups (Table 3).62-66 In patients with hypertension, diabetes or syn- drome X, the reduction in plasma ADMA achieved by ACE inhibition was in the range of 12-20%, while plasma L-arginine levels did not seem to be affected.63 ARBs were found to reduce plasma ADMA by 10-16%.62,66 All of these studies were small and had rather short observation periods of 1-12 weeks. Thus, confirmation of these promising results by larger trials will be required.

The results of a recent study in eNOS knockout mice suggests that ADMA may also exert NO-inde- pendent effects via upregulation of ACE and augmen- tation of oxidative stress through AT1-dependent pathways.67 Thus, ACE inhibitors and ARBs may help to prevent ADMA-induced pathology independently of their effects on plasma ADMA levels.

Hypoglycemic agents

In patients with type 2 diabetes, 3 months of treatment with 0.5-1.0 g/d metformin alone (n = 16) or in com- bination with sulfonylurea (n = 15) reduced plasma ADMA concentrations by [START_REF] Achan | all-trans-Retinoic acid increases nitric oxide synthesis by endothelial cells: a role for the induction of dimethylarginine dimethylaminohydrolase[END_REF].5% and 32.0% respec- tively.68 Some caution is warranted, however, as no placebo data are available from that study.

Furthermore, in contrast to what one would expect from the in vitro data, no relationship was observed between the decrease in ADMA concentration and glycemic control. Thus, it is possible that the reduc- tion of ADMA levels by metformin is mediated via glucose-independent mechanisms. In this respect it may be of interest to note that metformin has struc- tural similarities to ADMA.69

In an uncontrolled study the PPAR-gamma agonist rosiglitazone (12 weeks of treatment with a final dose of up to 8 mg/d) improved insulin sensitivity and reduced plasma ADMA concentrations by 30% in seven insulin-resistant patients.10 These data certainly await further confirmation by larger controlled trials because, in vitro, neither PPAR-gamma agonists (ciglitazone) nor PPAR-gamma antagonists (T007) significantly altered cellular ADMA liberation. [START_REF] Albsmeier | Bedeutang endogener Inhibitoren der NO-Synthase für kardiovaskuläre Erkrankungen und ihre pharmakologische Therapie (Relevance of endogenous NOS inhibitors for cardiovascular disease and its therapy)[END_REF] Apart from the effects on blood glucose there is, how- ever, at least support from theoretical considerations because a PPAR/PXR binding site has been identified in the promotor region of Hormone replacement therapy Hormone replacement therapy (HRT) has frequently been shown to improve endothelial function and NO synthesis.71,72 Moreover, ADMA levels were found to decrease in normal pregnancy.&dquo; The precise mecha- nism by which estrogen reduces ADMA has remained obscure so far. The effect of various forms of HRT on ADMA plasma concentration was explored in some small randomized controlled trials (Table 4).73-75 In all Table 3 Effect of ACE inhibitors and angiotensin receptor blockers on ADMA plasma concentration. aData extracted from graphs in publication. of these trials ADMA levels were modestly (5-21 %) reduced by 17-beta-estradiol alone or when sequentially combined with cyclogesterone or trimegestone. Unfortunately, L-arginine levels also declined, result- ing in no change or even a decrease in the L-arginine/ ADMA ratio. Thus, unless it can be proven that the decrease in L-arginine was the result of increased con- sumption in NO synthesis (and not upregulation of arginase activity), it remains questionable how much benefit can be conferred by HRT on patients with an elevated ADMA.

Conclusion and outlook

Specific ADMA-lowering therapies are not yet avail- able. Promising results from first pilot studies with widely used drugs such as ACE-inhibitors, ARBs, hypoglycemic agents and HRT await confirmation in large placebo-controlled trials.

To develop more specific therapies, further insights into the mechanisms leading to an elevation of ADMA in vivo are needed. Tools such as high-throughput methods for the quantification of ADMA and isoform- specific DDAH inhibitors (and activators) will play a key role. Important insights may also come from the DDAH-transgenic mice76 and DDAHI/2 knock out models currently under development. So far, most conditions associated with an elevation of ADMA are chronic, so ADMA-lowering therapies will have to be long term. Future studies will therefore have to address carefully the long-term effects of ADMA- lowering therapies on angiogenesis and tumor growth.

Until specific ADMA-lowering therapies become available, treatment of modifiable risk factors leading to elevation of ADMA or depletion of L-arginine, and supplementation with L-arginine, may be the best available options for patients with high plasma ADMA concentrations because NO synthesis is corre- lated with the L-arginine/ADMA ratio. [START_REF] Tsikas | Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine paradox[END_REF][START_REF] BöGer | The clinical pharmacology of L-arginine[END_REF]

Table 1

 1 Major sites of ADMA elimination. aEstimate based on rat data.

Table 2

 2 Effect of statin therapy on plasma ADMA levels. (ACE) inhibitors and angiotensin receptor blockers (ARBs) were found to improve endothelial function and NO availability.59-61 Several studies have assessed the effect of ACE inhibitors or ARBs on

	ns, not significant.

enzyme

Table 4

 4 Effect of hormone therapy on ADMA plasma concentration.

-, data not cited.