Cultural and social practices regarding menstruation among adolescent girls.

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Kumar, Anant; Srivastava, Kamiya

2011-01-01

The study attempts to find out the existing social and cultural practices regarding menstruation, awareness levels, and the behavioral changes that come about in adolescent girls during menstruation, their perception about menarche, how do they treat it, and the various taboos, norms, and cultural practices associated with menarche. The study was conducted on 117 adolescent girls (age 11-20 years) and 41 mothers from various communities and classes in Ranchi comprising residential colonies and urban slums. The findings unfolds many practices: cultural and social restrictions associated with menstruation, myth, and misconception; the adaptability of the adolescent girls toward it; their reaction, reaction of the family; realization of the importance of menstruation; and the changes that have come in their life after menarche and their resistance to such changes. The article also suggests the strategies to improve menstrual health and hygiene among adolescent girls. The study concludes that cultural and social practices regarding menstruation depend on girls' education, attitude, family environment, culture, and belief.

Menstruation-related Headache in Adolescents: Point Prevalence and Associated Factors.

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Carman, K B; Arslantas, D; Unsal, A; Atay, E; Ocal, E E; Demirtas, Z; Saglan, R; Dinleyici, M; Yarar, C

2018-04-02

To study the prevalence of menstruation-related headache and the impact of associated factors in adolescents. This cross-sectional study was conducted in seven randomly selected high schools, and 3,886 girls attending those schools were invited. After the consent of the school principals, a final total of 2,485 girls (63.9%) were involved in the study. A specific questionnaire was distributed to adolescent girls (14-19 years old). The first part of the survey investigated the features of menstruation (age of first menstruation, duration of period, pad fully soaked per day). The last part of the questionnaire surveyed the presence of headache during the menstruation period. The severity of headache was measured by a visual analogue scale. Lastly, participants were requested to complete the Beck Depression Inventory (BDI). The prevalence of menstruation-related headache and associated factors were studied. The mean age of the study group was 15.89 ± 1.07 (14-19) years old. The age of onset of menarche was younger than 12 years old in 32.4% of girls, and mean age of onset of menarche was 12.96 ± 1.09 years old. The prevalence of menstruation-related headache was calculated to be 25.9% (n = 646). The onset of menstruation before the age of 12 years old, longer duration of menstruation period, dysmenorrhea, daily consumption of coffee and cola and smoking significantly affected the frequency of menstruation-related headache. The mean scores of the BDI were calculated as 21.68 ± 13.65 and a significant relationship was found between headache and BDI scores. Our study indicates that menstruation-related headache is a common problem of adolescent girls. It might be associated with different comorbidities such as depression. Accordingly, a multidisciplinary treatment approach must be considered to improve their life quality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A missing piece: the spiny mouse and the puzzle of menstruating species.

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Bellofiore, Nadia; Cousins, Fiona; Temple-Smith, Peter; Dickinson, Hayley; Evans, Jemma

2018-07-01

We recently discovered the first known menstruating rodent. With the exception of four bats and the elephant shrew, the common spiny mouse ( Acomys cahirinus ) is the only species outside the primate order to exhibit menses. There are few widely accepted theories on why menstruation developed as the preferred reproductive strategy of these select mammals, all of which reference the evolution of spontaneous decidualisation prior to menstrual shedding. Though menstruating species share several reproductive traits, there has been no identifiable feature unique to menstruating species. Such a feature might suggest why spontaneous decidualisation, and thus menstruation, evolved in these species. We propose that a ≥3-fold increase in progesterone during the luteal phase of the reproductive cycle is a unique characteristic linking menstruating species. We discuss spontaneous decidualisation as a consequence of high progesterone, and the potential role of prolactin in screening for defective embryos in these species to aid in minimising implantation of abnormal embryos. We further explore the possible impact of nutrition in selecting species to undergo spontaneous decidualisation and subsequent menstruation. We summarise the current knowledge of menstruation, discuss current pre-clinical models of menstruation and how the spiny mouse may benefit advancing our understanding of this rare biological phenomenon. © 2018 Society for Endocrinology.

A Content Analysis of Educational Media about Menstruation.

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Havens, Beverly; Swenson, Ingrid

1989-01-01

Reviewed 31 audiovisual media for content related to physical and psychological aspects of menstruation; portrayal of adolescent girls, parents, and peers; and relationship of menstruation to developmental process. In general, variations in physical and emotional responses were described as normal. In all cases, fear and embarrassment were…

Attitudes and feelings towards menstruation and womanhood in girls at menarche.

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Rembeck, Gun I; Möller, Margareta; Gunnarsson, Ronny K

2006-06-01

To elucidate early adolescent girls' attitudes, thoughts and feelings towards menstruation and their bodies. 309 12-y-old girls answered questionnaires. One part of the questionnaire dealt with thoughts and feelings towards menstruation. The other part dealt with thoughts and feelings towards menstruation and sex and ability to communicate on aspects of womanhood. Postmenarcheal girls were less positive towards menstruation than premenarcheal girls (p = 1 x 10(-6)). Many girls (43%) did not reaffirm the statement "I like my body" and almost one quarter stated being teased for their appearance. Many of the girls claimed that they had been called "cunt" (38%) or "whore" (46%). If called "cunt" or "whore", 17% stated that they felt alone, 76% felt anger and 50% were offended. Mothers were those with whom girls could most easily "chat" about their period. Sixty-seven per cent received information about menstruation from school nurses. Wanting to be an adult and liking that their body develops seem to be associated with a more positive feeling towards menstruation. Furthermore, mothers' timing and ability to communicate attitudes towards menstruation and the body are as important as those in a girl's immediate environment.

School Absenteeism during Menstruation among Rural Adolescent Girls in Pune

OpenAIRE

Suman Bodat, Mrunalini M Ghate, Jyoti R Majumdar

2013-01-01

Background: Menstrual related problems and inadequate school sanitation facilities have an adverse effect on adolescent girl?s academic performance and school attendance especially in rural setting. The following study was undertaken to determine school absenteeism during menstruation period. Objective: To assess the impact of menstruation on school attendance and factors affecting menstruation management. Methods: This cross sectional study was conducted in rural field practice area o...

The increase in leucocyte count during menstruation is a function of ...

African Journals Online (AJOL)

Menstruation is an endocrine mediated physiologic cyclical bleeding per vagina in a non-pregnant woman of the reproductive age group. Blood is a good culture medium for bacteria and as such, menstruation can affect leucocytes count. This study is aimed at evaluating leucocytes count during menstruation. Fifty-eight ...

Taiwanese adolescents' gender differences in knowledge and attitudes towards menstruation.

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Cheng, Ching-Yu; Yang, Kyeongra; Liou, Shwu-Ru

2007-06-01

The purpose of the study was to explore gender differences in knowledge and attitudes towards menstruation among Taiwanese adolescents. This study was a secondary data analysis of a cross-sectional comparison study conducted in Taiwan. A total of 287 female and 269 male students at a junior high school participated in the study. The results showed that almost all the students had heard about menstruation and most of them had received menstrual information at school. However, their knowledge about menstruation was not accurate. Moreover, the male students expressed more negative attitudes towards menstruation than the female students. Taboos were heard by most students and, although many female students doubted the reality of the taboos they had heard, they observed them anyway. The study calls for an evaluation of sex education and suggests more open discussions about menstruation among young people in those education sessions. In addition, school nurses and obstetrical/gynecological nurses should be involved more in adolescents' sexual education.

[Comparative study of reflectance spectroscopy of women's acupoints around menstruation].

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Jiang, Xing-Hui; Liu, Han-Ping; Guo, Zhou-Yi; Meng, Yao-Yong; Zeng, Chang-Chun; Liu, Song-Hao

2010-12-01

Acupoint was reaction of viscera and its optical parameter was an important characteristic of tissue. In the present work, in order to discuss specificity of acupuncture on the response of qi and blood in human body, we compared the diffuse reflectance of Taichong (LV3), Taibai (SP3), and Chongyang (ST42) before, during and after menstruation. All the acupoints had the same shape of the spectrum and troughs were all at 423.16, 544.06 and 577.47 nm. The values of reflectance during menstruation were greater than before and after menstruation, especially for SP3 and ST42 (P menstruation. Diffuse reflectance may be possibly used in the quantitative analysis of qi and blood.

Attitudes Towards Menstruation.

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Stevens, Gwendolyn; Gardner, Sheldon

To explore current conceptions about menstruation, 50 male and female undergraduate students were asked to Q sort symptoms from the Moos Menstrual Distress Questionnaire (MDQ). The MDQ is a scale which contains 47 symptoms which have been associated with the menstrual cycle. The Q sort is a statistical technique in which data are analyzed as…

Attitudes toward menstruation in females with schizophrenia or schizoaffective disorders in Taiwan.

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Liang, H-Y; Lee, L-W; Kelsen, B A; Hsu, S-C; Liu, C-Y; Chen, C-Y

2013-12-01

The aims of this cross-sectional, case-controlled, observational study were to examine attitudes toward menstruation in female patients with schizophrenia or schizoaffective disorder and in a control group, and to explore the associations between attitudes toward menstruation and psychopathology, menstrual regularity during antipsychotic treatment, and menstrual distress symptoms. Fifty-eight patients treated with anti-psychotic medications for at least the previous 6 months were placed in irregular (irregular menstrual cycle) (n = 31) and regular (regular menstrual cycle) (n = 27) groups. Sixty-two, age-matched, healthy female participants with regular menstrual cycles were enrolled as a control group. Psychopathology was assessed by psychiatrists using the Positive and Negative Syndrome Scale (PANSS). The Menstrual Attitude Questionnaire (MAQ) was used to assess attitudes toward menstruation, and symptom checklists based on the Moos Menstruation Distress Questionnaire (MMDQ) were used to assess menstrual distress symptoms. Patients with psychotic disorders (both irregular and regular groups) had more negative attitudes toward menstruation than the control group. In the Schizophrenia group, there was no association between the severity of psychotic symptoms and their influence on attitudes toward menstruation. Moreover, regular menstrual cycles during antipsychotic treatment and fewer menstrual distress symptoms were the two main predictors for more positive attitudes toward menstruation in the patient group. This is one of the first studies to explore the relationship between psychotic symptoms and attitudes toward menstruation. The findings provide more support for the assumption that attitudes toward menstruation are derived from a woman's perception of her bodily experience rather than a psychiatric disorder.

Cultural aspects and mythologies surrounding menstruation and abnormal uterine bleeding.

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Tan, Delfin A; Haththotuwa, Rohana; Fraser, Ian S

2017-04-01

The objective of this chapter is to present an overview of how menstruation, a normal bodily function, was and is perceived in various ethnic groups and cultures in the world, from ancient mythology, historical, or traditional practices to contemporary belief systems. Mythical tales about menstruation abound in the legends and prehistory of ancient cultures. These tales characterize menstrual blood variously as sacred, a gift from the gods, or a punishment for sin, but it is almost always magical and powerful. In contrast, most world religions view menstruation, with varying degrees of severity, as a major problem, a sign of impurity and uncleanliness, and therefore, menstruating women are isolated, prohibited from polluting the holy places, and shunned. Many of these myths and cultural misperceptions persist to the present day, reflected in a wide range of negative attitudes toward menstruation, which can have serious and direct implications for reproductive health. In view of the increasingly globalized nature of current clinical practice, it is crucial that health care providers are familiar with existing cultural and social views and attitudes toward the menstrual function. The ultimate goal is to be able to provide women culturally sensitive and medically appropriate therapies for their menstrual disorders. This biocultural approach to menstruation management is desirable in contemporary medical practice. Copyright © 2016. Published by Elsevier Ltd.

Attitudes and practices of school-aged girls towards menstruation.

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Jarrah, Samiha Suhail; Kamel, Andaleeb Abu

2012-06-01

The purpose of this study was to (i) investigate attitude and menstruation-related practices in Jordanian school-aged girls; (ii) identify the influence of premenstrual preparation on girls' attitude and menstruation-related practices. A descriptive cross-sectional design was used. Data was collected from a convenience sample of 490 school-age girls (12-18 years) from different districts in Jordan. Self-report instruments [Menstrual Attitude Questionnaire (MAQ), and Menstrual Practices Questionnaires (MPQ)] were used to assess the study variables. Descriptive statistics, correlation and chi-square tests were used to analyze the data. It was found that menstrual attitude and practices were positively correlated. Poor attitude toward menstruation and low menstrual practices were significantly associated with inadequate premenstrual preparation. There is a need to prepare girls for menstruation before menarche. The role of the schools and teachers should be reinforced through formal and well planned reproductive health educators for girls and their mothers. © 2012 Blackwell Publishing Asia Pty Ltd.

Menstruation, perimenopause, and chaos theory.

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Derry, Paula S; Derry, Gregory N

2012-01-01

This article argues that menstruation, including the transition to menopause, results from a specific kind of complex system, namely, one that is nonlinear, dynamical, and chaotic. A complexity-based perspective changes how we think about and research menstruation-related health problems and positive health. Chaotic systems are deterministic but not predictable, characterized by sensitivity to initial conditions and strange attractors. Chaos theory provides a coherent framework that qualitatively accounts for puzzling results from perimenopause research. It directs attention to variability within and between women, adaptation, lifespan development, and the need for complex explanations of disease. Whether the menstrual cycle is chaotic can be empirically tested, and a summary of our research on 20- to 40-year-old women is provided.

Menstrual socialization, beliefs, and attitudes concerning menstruation in rural and urban Mexican women.

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Marvan, Maria Luisa; Trujillo, Paulina

2010-01-01

Women living in rural and urban areas of Mexico answered a questionnaire about what they were told at home about menstruation before their menarche (first menstruation), and answered the Beliefs About and Attitudes Toward Menstruation Questionnaire. Around half of both urban and rural women were told that they were going to experience negative perimenstrual changes. There were fewer urban than rural women who were advised to do or not to do certain activities while menstruating. Menstrual socialization affected the beliefs and attitudes concerning menstruation held by women as adults. These findings are discussed in light of the sociocultural background of the participants.

Statistical testing of association between menstruation and migraine.

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Barra, Mathias; Dahl, Fredrik A; Vetvik, Kjersti G

2015-02-01

To repair and refine a previously proposed method for statistical analysis of association between migraine and menstruation. Menstrually related migraine (MRM) affects about 20% of female migraineurs in the general population. The exact pathophysiological link from menstruation to migraine is hypothesized to be through fluctuations in female reproductive hormones, but the exact mechanisms remain unknown. Therefore, the main diagnostic criterion today is concurrency of migraine attacks with menstruation. Methods aiming to exclude spurious associations are wanted, so that further research into these mechanisms can be performed on a population with a true association. The statistical method is based on a simple two-parameter null model of MRM (which allows for simulation modeling), and Fisher's exact test (with mid-p correction) applied to standard 2 × 2 contingency tables derived from the patients' headache diaries. Our method is a corrected version of a previously published flawed framework. To our best knowledge, no other published methods for establishing a menstruation-migraine association by statistical means exist today. The probabilistic methodology shows good performance when subjected to receiver operator characteristic curve analysis. Quick reference cutoff values for the clinical setting were tabulated for assessing association given a patient's headache history. In this paper, we correct a proposed method for establishing association between menstruation and migraine by statistical methods. We conclude that the proposed standard of 3-cycle observations prior to setting an MRM diagnosis should be extended with at least one perimenstrual window to obtain sufficient information for statistical processing. © 2014 American Headache Society.

Transient trimethylaminuria related to menstruation

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Shimizu, Makiko; Cashman, John R; Yamazaki, Hiroshi

2007-01-01

Background Trimethylaminuria, or fish odor syndrome, includes a transient or mild malodor caused by an excessive amount of malodorous trimethylamine as a result of body secretions. Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3). Methods FMO3 metabolic capacity (conversion of trimethylamine to trimethylamine N-oxide) was defined as the urinary ratio of trimethylamine N-oxide to total trimethylamine. Results Self-reported Case (A) that was homozygous for inactive Arg500stop FMO3, showed decreased metabolic capacity of FMO3 (i.e., ~10% the unaffected metabolic capacity) during 120 days of observation. For Case (B) that was homozygous for common [Glu158Lys; Glu308Gly] FMO3 polymorphisms, metabolic capacity of FMO3 was almost ~90%, except for a few days surrounding menstruation showing 90%) metabolic capacity, however, on days around menstruation the FMO3 metabolic capacity was decreased to ~60–70%. Conclusion Together, these results indicate that abnormal FMO3 capacity is caused by menstruation particularly in the presence, in homozygous form, of mild genetic variants such as [Glu158Lys; Glu308Gly] that cause a reduced FMO3 function. PMID:17257434

Women's attitudes about menstruation and associated health and behavioral characteristics.

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Morrison, Lynn A; Larkspur, Louona; Calibuso, Marites J; Brown, Susan

2010-01-01

To examine the relationships between attitudes towards menstruation, health, and behavioral characteristics. The 136 women who completed questionnaires varied in their sexual activity, sexual orientation, and use of hormonal contraception. Women's estimated cycle length was accurate when compared to observed cycle length (F (3,156) = .05; P = .98). Smokers had decreased durations of flow (P menstruation as natural compared to abstinent, sexually active heterosexuals or those using traditional oral contraception (F (5,141) = 2.43; P = .04). Hormonal contraception use, but not sexual orientation, was associated with attitudes about menstruation.

Place of menstruation in the reproductive lives of women of rural North India

Directory of Open Access Journals (Sweden)

Singh A

2006-01-01

Full Text Available Objective : To ascertain the perceptions and experiences of women regarding menstruation. Methods : An integrated qualitative and quantitative study on reproductive health of Indian women was conducted in two primary health centre areas of rural north India. Present article reports on the perceptions of 1205 women regarding various aspects of menstruation. Results : Major source of information about menarche/menstruation was friends/relatives (72%. Mean age at menarche was ~ 15 years. Very few women (0.4% used sanitary napkins. Majority of women had strong beliefs about effect of diet on menstruation. Most of them considered menstruation a dirty act and indulged in various taboo behaviours. Initial reaction was of fear/apprehension at menarche in majority of girls. Conclusion: Women in rural north India still hold tranditional beliefs regarding menstruation. Provision of a balanced and healthy family health education package to all girls is recommended.

Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.

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Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D

2018-01-23

Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

[Survey on menopausal age and menstruation span in women in Pudong district of Shanghai].

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Chen, Hua; Feng, You-ji; Shu, Hui-min; Lu, Tian-mei; Zhu, Hong-mei; Yang, Bin-lie; Xiong, Miao

2010-06-01

To investigate natural spontaneous menopausal age, menstruation span and their relationship with menarche age and parity in Pudong district of Shanghai. From Jan 2007 to Jul 2008, 15 083 spontaneous menopause women undergoing cervical cancer screening were enrolled in this study. The questionnaire included menarche age, parity, spontaneous menopausal age and menstruation span. Those women were divided into four groups based on age, which were group of 56 - 60, 61 - 65, 66 - 70 and more than 70.Analysis of variance (ANOVA) was used for comparing difference between menopausal age and menstruation span. Multiple factor regressions was used to analyze the relationship between menarche age, parity and menopausal age and menstruation span. (1) Spontaneous menopausal age: the minimum was 29 years old, the maximum was 61 years old, and the mean age was (50.6 ± 3.7) years old. The mean spontaneous menopause age were (50.9 ± 3.4), (50.7 ± 3.7), (50.0 ± 4.1), (49.6 ± 4.0) years in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menopausal age were observed, which the difference of 1.36 year was shown between groups of 56 - 60 and more than 70 years. (2) Menstruation span: the mean of menstruation span was (34.3 ± 4.1) years, which the minimal age of 12 years and maximal age of 48 years were recorded. (34.6 ± 3.8), (34.3 ± 4.1), (33.9 ± 4.6), (33.2 ± 4.5) were observed in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menstruation span were observed, which the difference of 1.41 year was shown between groups of 56 - 60 and more than 70 years. (3) The impact of menarche age on menopausal age and menstruation span: there was no correlation between menarche age and menopausal age (r = 0.02); however, menstruation span was found to be negatively correlated with the menarche age (r = -0.43). (4) The impact

Menstruation experiences of South African women belonging to the ama-Xhosa ethnic group.

Science.gov (United States)

Padmanabhanunni, Anita; Jaffer, Labeeqah; Steenkamp, Jeanette

2017-09-15

A growing body of research has emphasised the salience of cultural beliefs and traditional practices to women's experiences of menstruation. Relatively less research has, however, been undertaken in South Africa. This study explored the experience of menstruation among women from the ama-Xhosa ethnic group, one of the largest ethnic groups in the country. Among the ama-Xhosa, there are distinct cultural practices associated with menstruation, including the female rite of passage (intonjane) and virginity testing (inkciyo). However, few studies have explored the experience of menstruation for women from this cultural group. This study involved the synthesis of data from individual interviews and focus group discussions conducted among a sample of ama-Xhosa women. The data were analysed using thematic analysis. Distinctive findings included women's participation in traditional cultural practices of intonjane and inkciyo and the presence of cultural taboos associated with menstruation. Women's narratives revealed strong ambivalence regarding these practices. On the one hand, they wanted to adhere to traditional practices but experienced these customs as evoking discomfort and shame. The study confirmed the prevalence of negative constructions of menstruation. Positive appraisals of menstruation as evoking joy and happiness were also encountered.

Menstruation: symptoms, management and attitude of female nursing students in Ibadan, Nigeria.

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Moronkola, O A; Uzuegbu, V U

2006-12-01

This study surveyed 120 student nurses from two schools of nursing in Ibadan, Nigeria to assess the symptoms experienced during menstruation, attitude towards and management of menstruation. The student nurses overall mean age at menarche was 14 years, average duration of menstrual period was five days and mean of menstrual cycle was 28 days. Out of the 120 study participants, 93% were having menstruation regularly. More participants experienced symptoms during premenstrual periods than menstrual periods. Majority (70%) used sanitary pad to manage their menstruation, 93% had positive attitude towards menstruation while only 20% consulted medical doctors whenever they experienced menstrual symptoms. Paracetamol was the drug of choice for many of the participants whenever they experienced menstrual symptoms It was recommended that authorities in schools of nursing should not overlook reproductive health needs of students. Also teaching of reproductive health education early in primary and secondary schools should be encouraged.

Young Adolescents' Beliefs Concerning Menstruation

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Clarke, Anne E.; Ruble, Diane N.

1978-01-01

A sample of 54 young adolescent girls (both pre- and postmenarcheal) and boys responded to a questionnaire assessing evaluative attitudes toward menstruation, expected symptomatology, perceived effects on moods and activities, and sources of information for these beliefs. (Author/JMB)

Perceptions and practices on menstruation amongst Nigerian secondary school girls.

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Adinma, Echendu Dolly; Adinma, J I B

2008-04-01

This cross-sectional descriptive study was conducted amongst 550 secondary school girls in southeastern Nigeria to determine their perceptions, problems, and practices on menstruation. Majority of the students, (75.6%), were aged 15-17 years. Only 39.3% perceived menstruation to be physiological. Abdominal pain/discomfort, (66.2%), was the commonest medical problem encountered by the respondents, although 45.8% had multiple problems. Medical problems were most commonly discussed with the mother, (47.1%), and least commonly discussed with the teachers, 0.4%. Analgesics, (75.6%), were most commonly used to relieve menstrual pain. Only 10% of respondents used non-pharmacologic remedies. Unsanitary menstrual absorbents were used by 55.7% of the respondents. Menstruation perceptions are poor, and practices often incorrect. A multi-dimensional approach focusing on capacity building of mothers, and teachers on sexuality education skills; using religious organizations as avenues for sexuality education; and effectively using the Mass Media as reproductive health education channels are recommended towards improving adolescents' perceptions and practices on menstruation.

Molecular and functional aspects of menstruation in the macaque.

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Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Age at menarche, reactions to menarche and attitudes towards menstruation among Mexican adolescent girls.

Science.gov (United States)

Marván, Ma Luisa; Alcalá-Herrera, Verónica

2014-04-01

To investigate the relationships between menarcheal timing and both menarcheal experience and attitudes toward menstruation in Mexican girls. Cross-sectional survey. Sample of adolescents attending 10 different public schools. Mexican postmenarcheal adolescents, aged 11-16 years. Participants answered 1 questionnaire about menarcheal experience and another about attitudes towards menstruation. Early maturers (menarche before 11 years) were more likely than average (menarche at 11 or 12 years) or late maturers (menarche at 13 or more years) to state they had not known what they should do at the moment they got their first period (P menstruating (P menstruation (P menstruation than their peers (P menstruation. Since these girls have limited or in some cases no time for preparation, they need special support. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The role of menstruation in women's objectification: a questionnaire study.

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Sveinsdóttir, Herdís

2017-06-01

The aim of this study was to investigate the concepts of objectification and self-objectification among young women in the context of attitudes towards menstruation, menstrual suppression, menstrual and menarche experiences, disorder eating and exercise habits and to detect predictors of objectification and self-objectification. The negative effects of objectification are well founded. Considering the central role menstruation plays in female biology, it comes as quite a surprise that so little attention is given to the subject in the research on objectification. Cross-sectional explorative survey design. A questionnaire that included the Self-Objectification Questionnaire, the Objectified Body Consciousness Scale, the Belief and Attitudes Towards Menstruation Questionnaire and the Suppress Menstruation subscale of the Attitudes Towards Menstrual Suppression Questionnaire was administered at the end of 2013 to 319 Icelandic women who represented the population by age. A stepwise multiple linear regression model was employed to calculate significant predictors of objectification and self-objectification. Four models of objectification are presented: the self-objectification model, the body surveillance model, the body shame model and the control belief model. Taken together, the strongest predictors of these models were related to eating habits. However, the findings also support the proposition that menstrual-related experiences influence women's objectification, particularly in terms of age at menarche, of belief in the prescriptive role of menstruation and of use of pain medication for menstrual pain. Healthcare providers in general and nurses in particular could and should assist girls and women in developing a positive view of their body and its reproductive functions by discussing the body and menstruation based on women's concerns. © 2016 John Wiley & Sons Ltd.

Queer periods: attitudes toward and experiences with menstruation in the masculine of centre and transgender community.

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Chrisler, Joan C; Gorman, Jennifer A; Manion, Jen; Murgo, Michael; Barney, Angela; Adams-Clark, Alexis; Newton, Jessica R; McGrath, Meaghan

2016-11-01

Menstruation has long been viewed as an important aspect of women's health. However, scholars and healthcare providers have only recently begun to recognise that transgender men and people with masculine gender identities also menstruate, thus little is known about their attitudes toward and experiences with menstruation. A sample of masculine of centre and transgender individuals with a mean age of 30 years was recruited online to complete measures of attitudes toward menstruation and menstrual suppression and to answer exploratory questions about their experiences managing menstruation. Participants reported mixed attitudes toward menstruation, but generally positive attitudes toward menstrual suppression. Many participants said that they try to avoid public restrooms during menstruation because of practical and psychological concerns. Implications of our findings for the transgender health are discussed.

'We do not know': a qualitative study exploring boys perceptions of menstruation in India.

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Mason, Linda; Sivakami, Muthusamy; Thakur, Harshad; Kakade, Narendra; Beauman, Ashley; Alexander, Kelly T; van Eijke, Anna Maria; Laserson, Kayla F; Thakkar, Mamita B; Phillips-Howard, Penelope A

2017-12-08

In low-middle income countries and other areas of poverty, menstrual hygiene management (MHM) can be problematic for women and girls. Issues include lack of knowledge about menstruation and MHM, and stigma around menstruation, also access to affordable and absorbent materials; privacy to change; adequate washing, cleaning and drying facilities; as well as appropriate and accessible disposal facilities. In order to effect change and tackle these issues, particularly in patriarchal societies, males may need to become advocates for MHM alongside women. However, little is known about their knowledge and attitudes towards menstruation, which may need addressing before they can assist in acting as advocates for change. The present study was undertaken to explore knowledge and attitudes about menstruation among adolescent boys across India, in order to gauge their potential to support their 'sisters'. The study was undertaken across three states in India, chosen a priori to represent the cultural and socio-economic diversity. Qualitative data using focus group discussions with 85 boys aged 13-17 years, from 8 schools, was gathered. Data were analysed using thematic analysis. The results were organised into three main themes, reflecting the key research questions: boys' knowledge of menstruation, source of knowledge, and attitudes towards menstruation and menstruating girls. Knowledge comprised three aspects; biological function which were generally poorly understood; cultural rites which were recognized by all; and girls' behaviour and demeanour, which were noted to be withdrawn. Some boys learnt about puberty and menstruation as part of the curriculum but had concerns this was not in-depth, or was missed out altogether. Most gathered knowledge from informal sources, from overhearing conversations or observing cultural rituals. Few boys openly displayed a negative attitude, although a minority voiced the idea that menstruation is a 'disease'. Boys were mostly sympathetic

Reversible Suppression of Menstruation with Antiprogestins

National Research Council Canada - National Science Library

Brenner, Robert

2000-01-01

...) are compounds that bind to the P receptor and block P action. Continuous blockade of P action during the menstrual cycle by PAs would prevent progestational priming of the endometrium and thus inhibit menstruation...

Menstruation in Ulysses.

Science.gov (United States)

Mullin, Katherine

2008-01-01

This article investigates James Joyce's fascination with a wide variety of medical texts, sexual folklores, religious beliefs, and persistent superstitions about menstruation. That fascination finds its way into Ulysses, which draws upon a number of intertexts to inform a curiosity about the female body most strikingly articulated by Bloom, Molly, and Gerty MacDowell. These intertexts are not simply imported into the novel but are dismantled and interrogated, as Joyce exposes, rather than endorses, clichés of essential femininity.

Subclinical impairment of ovarian reserve in systemic lupus erythematosus patients with normal menstruation not using alkylating therapy.

Science.gov (United States)

Ma, Wenhong; Zhan, Zhongping; Liang, Xiaoyan; Chen, Jianhui; Huang, Xingfang; Liao, Caiyun

2013-12-01

Disease activity is a major factor in menstrual disorders in systemic lupus erythematosus (SLE) patients not receiving alkylating therapy. However, the ovarian reserve of SLE women with normal menstruation is still unclear. Twenty-three SLE patients naïve to cytotoxic agents (SLE group) and nineteen SLE patients receiving current or previous cyclophosphamide (CTX) therapy (without other cytotoxic agents; SLE-CTX group) were enrolled. Twenty-one age-matched healthy women served as controls. All patients and controls had a regular menstrual cycle. Basal hormone levels, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), and antral follicle count (AFC) were analyzed in the two study groups and compared with the control group. No significant differences were found between the SLE, SLE-CTX, and control groups in age, body mass index (BMI), and basal FSH and LH levels. The E2 (P=0.023) levels were high and the AMH (P=0.000) values and AFC (P=0.001) were significantly lower in the SLE and SLE-CTX groups compared to control. However, these values were similar between the SLE and SLE-CTX groups. SLE patients not receiving alkylating therapy who had normal menstruation and short illness duration still had an impaired ovarian reserve.

Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients

Science.gov (United States)

Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

2016-01-01

Abstract Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26–55 years) and the median duration of follow-up was 64 months (range, 28–100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m2. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

Science.gov (United States)

Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

2016-04-01

Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis.

[Menstruation disorders more frequent in women with a history of sexual abuse

NARCIS (Netherlands)

Vink, C.W.; Labots-Vogelesang, S.M.; Lagro-Janssen, A.L.M.

2006-01-01

OBJECTIVE: To determine the relationship between menstruation disorders and prior sexual abuse. DESIGN: Questionnaire investigation. METHOD: A questionnaire was developed consisting of 50 questions about menstruation disorders, premenstrual syndrome and sexual abuse. The questionnaire was mailed to

Recurrent episcleritis in relation to menstruation: a case report.

Science.gov (United States)

Rajoo, Sangeetha Govinda; Gandhewar, Jaishree

2011-09-01

To describe a case of recurrent episcleritis associated with a patient's menstrual cycle. A retrospective case review of a 39-year-old woman who presented with a 12-year history of recurrent episcleritis in relation to her menstruation. She was seen during an acute attack and started on a reducing regime of topical steroids for 5 weeks. She was then advised to use it a week before and after menstruation. Examination and investigations revealed episcleritis with a negative systems review. After starting the treatment, she was symptom free when reviewed at 4, 8, 14, and 33 weeks. Now, the patient uses topical steroids only 1 week before menstruation. Literature review revealed no recent case reports and provided insufficient evidence to understand this relationship. We recommend increased awareness and reporting because there is a need for more studies to understand this relationship and to provide evidence for management.

Adolescent girls define menstruation: a multiethnic exploratory study.

Science.gov (United States)

Orringer, Kelly; Gahagan, Sheila

2010-09-01

Incomplete understanding of menstruation may place girls at risk for sexually transmitted diseases (STDs) and unintended pregnancy. Prior research suggests that European American and African American girls incompletely understand menstruation, yet little is known about menstrual knowledge in other ethnic groups. Using audiotaped focus group and individual interviews with 73 African American, Mexican American, Arab American, and European American girls, we assessed girls' menstrual understanding. Responses included reproduction, growing up, cleansing, messages about femininity, and not knowing. We found ethnic differences in the prominence of these themes. We learned that social and cultural factors play an important role in transmission of menstrual knowledge.

Menstruation, objectification and health-related quality of life: A questionnaire study.

Science.gov (United States)

Sveinsdóttir, Herdís

2018-02-01

To explore young women's health-related quality of life (HRQOL) and investigate whether menstrual and menarche experiences and objectification predict mental and physical health components of HRQOL. Menstruation plays a fundamental role in female biology, in women's relationship to their bodies and consequently in women's health and their HRQOL. Cross-sectional explorative survey design. A questionnaire that included the SF-36v2, the Self-objectification Questionnaire (SOQ), the Body Surveillance and Body Shame subscales of the Objectified Body Consciousness Scale, the Belief and Attitudes Towards Menstruation Questionnaire (four subscales), and questions on menarche and menstruation was administered at the end of 2013 to 319 Icelandic women who represented the population by age. The SF-36v2 includes eight dimensions addressing the mental and physical components of HRQOL. Scores are presented as raw data scores and scores based on standardised score of American women and range from 0 to 100 with higher scores indicating better HRQL. A hierarchical multiple linear regression model was employed to calculate significant predictors of mental and physical health components of HRQOL. Mean raw data scores on SF36-v2 dimensions ranged from 54.7 to 91.5. The participants scored below the standardised, mean norm-based score for all dimensions. Secrecy of menstruation, experience of body shame and pain during menstruation predicted worse mental HRQOL. To believe in the proscriptive role and the unpleasantness of menstruation, experience of body shame, medication for menstrual pain and not holding a university education predicted worse physical HRQOL. These two models explained 30% and 22% of the variance of the mental and physical components of SF36-v2, respectively. Young women's mental and physical HRQOL is influenced by the specific context of their lives. Women's health education should take into account the various relationships women may have with their bodies. © 2017

Experiences and Constructions of Menarche and Menstruation Among Migrant and Refugee Women.

Science.gov (United States)

Hawkey, Alexandra J; Ussher, Jane M; Perz, Janette; Metusela, Christine

2017-08-01

Experiences and constructions of menarche and menstruation are shaped by the sociocultural environment in which women are embedded. We explored experiences and constructions of menarche and menstruation among migrant and refugee women resettled in Sydney, Australia, and Vancouver, Canada. Seventy-eight semistructured individual interviews and 15 focus groups comprised of 82 participants were undertaken with women from Afghanistan, Iraq, Somalia, South Sudan, Sudan, Sri Lanka, and varying South American countries. We analyzed the data using thematic decomposition, identifying the overall theme "cycles of shame" and two core themes. In "becoming a woman," participants constructed menarche as a marker of womanhood, closely linked to marriage and childbearing. In "the unspeakable," women conveyed negative constructions of menstruation, positioning it as shameful, something to be concealed, and polluting. Identifying migrant and refugee women's experiences and constructions of menarche and menstruation is essential for culturally safe medical practice, health promotion, and health education.

Association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012

Science.gov (United States)

Mohamadirizi, Soheila; Kordi, Masoumeh

2013-01-01

Background: Menstruation signs are among the most common disorders in adolescents and are influenced by various environmental and psychosocial factors. This study aimed to define the association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012. Materials and Methods: This was a cross-sectional study on 407 high school girls in Mashhad who were selected through two-step random sampling. The students completed a questionnaire concerning demographic characteristics, menstruation, Depression, Anxiety, and Stress Scale of 21 questions (DASS-21), and menstruation signs in three phases of their menstruation. Data were analyzed by the statistical tests of Pearson correlation coefficient, Student's t-test, one-way analysis of variance (ANOVA), and regression through SPSS version 14. Results: Based on the findings, 74% of the subjects reported pre-menstruation signs, 94% reported signs during bleeding, and 40.8% reported post-menstruation signs. About 44.3% of the subjects had anxiety, 45.5% had depression, and 47.2% had stress. In addition, Pearson correlation coefficient test showed a significant positive correlation between menstruation signs and depression, anxiety, and stress (P menstruation signs and psycho-cognitive variables, prevention and treatment of these disorders by the authorities of education and training and the Ministry of Health are essential. PMID:24403944

Association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012.

Science.gov (United States)

Mohamadirizi, Soheila; Kordi, Masoumeh

2013-09-01

Menstruation signs are among the most common disorders in adolescents and are influenced by various environmental and psychosocial factors. This study aimed to define the association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012. This was a cross-sectional study on 407 high school girls in Mashhad who were selected through two-step random sampling. The students completed a questionnaire concerning demographic characteristics, menstruation, Depression, Anxiety, and Stress Scale of 21 questions (DASS-21), and menstruation signs in three phases of their menstruation. Data were analyzed by the statistical tests of Pearson correlation coefficient, Student's t-test, one-way analysis of variance (ANOVA), and regression through SPSS version 14. Based on the findings, 74% of the subjects reported pre-menstruation signs, 94% reported signs during bleeding, and 40.8% reported post-menstruation signs. About 44.3% of the subjects had anxiety, 45.5% had depression, and 47.2% had stress. In addition, Pearson correlation coefficient test showed a significant positive correlation between menstruation signs and depression, anxiety, and stress (P menstruation signs and psycho-cognitive variables, prevention and treatment of these disorders by the authorities of education and training and the Ministry of Health are essential.

What They Should Know About Menstruation.

Science.gov (United States)

McNab, Warren L.

1985-01-01

Lists common misconceptions about menstruation and suggests a unit on menstrual education. Activities and guidelines are presented along with unit outline. The outline consists of six major areas: definition and purpose; history; anatomy and reproduction; physiology; protection and discomfort; and related topics. (DH)

Structural changes in endometrial basal glands during menstruation.

Science.gov (United States)

Garry, R; Hart, R; Karthigasu, K A; Burke, C

2010-09-01

To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration. Prospective observational study. The academic gynaecological endoscopy unit of a university teaching hospital. Population Thirteen patients investigated for a variety of benign, non-infective gynaecological disorders during the active bleeding phase of the menstrual cycle. The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki-67 proliferation marker and the CD68 marker of macrophage activity. Change in morphology of endometrial glands at various stages of menstruation. Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki-67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss. Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki-67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.

Imagery associated with menstruation in advertising targeted to adolescent women.

Science.gov (United States)

Havens, B; Swenson, I

1988-01-01

Education about menstruation is not restricted to school instruction or information provided by adults and peers; exposure to advertisements in teen media provides imagery depicting menstruation and feminine role expectations. This paper analyzes the imagery in advertisements for sanitary products and products for the relief of menstrual symptoms. A 25% random sample of Seventeen magazine issues from 1976 to 1986 stratified by year were reviewed. A total of 135 ads for sanitary products and 32 ads for products for the relief of menstrual discomfort were analyzed. Each ad was examined for recurrent themes in text, context and tone. Data collected were examined for similarities in themes across both product type and time. The ads depict menstruation as a "hygienic crisis" that is best managed by an effective "security system" affording protection and "peace of mind." The failure of adequate protection places the woman at risk for soiling, staining, embarrassment and odor. Menstruating women are depicted as dynamic, energetic and always functioning at their optimal level. Such imagery may encourage guilt and diminished self-esteem in the adolescent who experiences discomfort. A lack of maternal, teacher or male figures in the ads is evident; the importance of peer support is reinforced.

Study on the Argument of "Menstruation" in Late Nineteenth-Century America : Focusing on M. P. Jacobi's The Question of Rest for Women during Menstruation

OpenAIRE

横山, 美和

2012-01-01

This article examines the argument concerning “menstruation” in late nineteenth-century America. With regard to an expansion of women's higher education, Sex in Education (1873) by Dr. Edward Clarke generated a controversy by stating that young women needed rest during menstruation; therefore the rigor of higher education would fail their health. Dr. Mary Putnam Jacobi refuted this argument in The Question of Rest for Women during Menstruation (1877). She attempted to combat the male research...

Managing Menstruation: Moderating Role of Symptom Severity on Active Coping and Acceptance.

Science.gov (United States)

Kennett, Deborah J; O'Hagan, Fergal T; Meyerhoff, Tanya J

2016-05-01

Although research has examined women's thoughts toward menstruation, the role passive and active coping strategies play in the acceptance of menses and getting-on with daily activities remains relatively unexplored. In total, 217 undergraduate females having normal regular monthly menstrual periods completed inventories assessing severity of menstrual symptoms, cognitive and emotional representation of health state, general and specific coping strategies, and acceptance. It was found that women having a more emotionally focused representation of menstruation (passive coping style) had a heightened belief that menstruation is debilitating and bothersome and, regardless of symptom severity, scored lower in acceptance of menstruation. Conversely, women using more active strategies to cope with menstrual symptoms were observed to be more generally resourceful and to conjunctively use more palliative coping strategies. More importantly, for women experiencing high levels of menstrual discomfort, use of active coping was associated with better acceptance and getting-on with everyday activities. © The Author(s) 2015.

Cultural practices relating to menarche and menstruation among adolescent girls in Taiwan--qualitative investigation.

Science.gov (United States)

Liu, H-L; Chen, K-H; Peng, N-H

2012-02-01

The aim of this study was to qualitatively record the cultural attitudes and practices associated with menarche and menstruation in Taiwanese girls, particularly with respect to coping mechanisms. Forty-eight adolescent girls participated. Adolescent girls were individually interviewed to investigate the effects of their cultural practices, coping mechanisms, and physiological symptoms during menarche and menstruation. The qualitative investigation revealed mixed reactions to menstruation, such as eating chocolate, using sanitary napkins, and feeling irritable or embarrassed. Cluster construction suggested that adolescents were prepared for menarche but required emotional support; in addition, the new generation employed the Internet to learn how to cope. A phenomenological approach showed that menarche and menstrual attitudes among Taiwanese adolescents were comprised in 4 dimensions: self-perception, information, and cultural practices with regard to menarche; physiological symptoms and psychological reactions during menstruation; coping mechanisms during menarche and menstruation; and methods for coping and cultural practices for menstruation. Cultural beliefs and the Internet have changed cross-cultural contacts. Educators and health professionals should seek to understand this generation of girls, who perceive the world as more flexible and available and have more creativity and new eating behaviors and hobbies. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Relationship between Female University Students' Knowledge on Menstruation and Their Menstrual Hygiene Practices: A Study in Tamale, Ghana

Science.gov (United States)

Garti, Helene Akpene

2016-01-01

Positive perception about menstruation and good menstrual hygiene practice safeguards the health of postpubescent females by reducing their vulnerability to reproductive and urinary tract infections. Using a questionnaire, a cross-sectional study involving 293 randomly selected female undergraduate students in northern Ghana assessed the relationship between knowledge on menstruation and the practice of safe menstrual hygiene. Data collected was analyzed using GraphPad 5.01. This study found that although majority of respondents (73.4%) were aware of menstruation before menarche, most of them experienced fear and panic when it occurred. Mothers were the first to be informed when menstruation occurred, although teachers first provided them knowledge on menstruation. Respondents' knowledge on menstruation was average (57.3%) but their menstrual hygiene practice was good (80.2%). Age (p = 0.005) and course of study (p = 0.0008) significantly influenced respondents' knowledge on menstruation with older students as well as the medical and midwifery students being most knowledgeable. Muslim rather than Christian female students practiced better menstrual hygiene (p = 0.0001). Average knowledge score on menstruation indicated a deficit of knowledge on the anatomy and physiology of the female reproductive system. Increasing knowledge on menstruation had a positive and significant effect on practice of good menstrual hygiene. PMID:27525125

Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

Directory of Open Access Journals (Sweden)

Astrid Menning

Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

A Case for Critical Literacy Analysis of the Advertising Texts of Menstruation: Responding to Missed Opportunities

Science.gov (United States)

Agnew, Shire; Sandretto, Susan

2016-01-01

When Agnew found the same, largely negative, dominant discourses of menstruation present in classroom lessons that researchers have been identifying for over 30 years, she sought different approaches to menstruation education. In this article the authors highlight the power of the media to (re)construct dominant discourses of menstruation and the…

Males Perform Better in Identifying Voices During Menstruation Than Females: A Pilot Study.

Science.gov (United States)

Wang, Xue; Xu, Xin; Liu, Yangyang

2016-10-01

The objective of the present study is to investigate gender differences in the ability to identify females' voice during menstruation. In Study 1, 55 male participants (M age = 19.6 years, SD = 1.0) were asked to listen to vocal samples from women during both ovulation and menstruation and to identify which recordings featured menstruating women. The results showed that the accuracy of men's responses (M = 56.73%, SD = 0.21) was significantly higher than 50%. In Study 2, 118 female students (M age = 19.4 years, SD = 1.6) completed the same task. The results indicated that the accuracy of women's performance was nearly 50%. These preliminary findings suggest that men are better able to identify women's voices during menstruation than women. Future work could consider several significant variables for the purpose of validating the results. © The Author(s) 2016.

[Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

Science.gov (United States)

Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

2016-09-25

Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively( P 12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P > 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of

Caring for a Daughter with Intellectual Disabilities in Managing Menstruation: A Mother's Perspective

Science.gov (United States)

Chou, Yueh-Ching; Lu, Zxy-Yann Jane

2012-01-01

Background: The concerns of mothers and their experiences while providing help to their daughters with intellectual disability (ID) and considerable support needs during menstruation have rarely been addressed. This qualitative study explored mothers' experiences and perceptions of managing their daughters' menstruation. Method: Twelve Taiwanese…

Redesigning Menstrual Education Programs Using Attitudes toward Menstruation.

Science.gov (United States)

Kieren, Dianne K.

1992-01-01

Critiques current menstrual education efforts and reviews current data about the nature of adolescent girls' attitudes toward menstruation as the basis for redesigning comprehensive, effective menstrual education programs. (Author)

Exacerbation of Behçet's syndrome and familial Mediterranean fever with menstruation.

Science.gov (United States)

Guzelant, Gul; Ozguler, Yesim; Esatoglu, Sinem Nihal; Karatemiz, Guzin; Ozdogan, Huri; Yurdakul, Sebahattin; Yazici, Hasan; Seyahi, Emire

2017-01-01

Menstruation triggers several conditions such as migraine, recurrent aphthous stomatitis and acne vulgaris in healthy individuals. There is evidence that Behçet's syndrome (BS) and familial Mediterranean fever (FMF) may exacerbate during menstruation. The aim is to assess whether BS and FMF patients experience menstrual flares. Females of reproductive age with BS and FMF seen consecutively at the outpatient clinic of Cerrahpasa Medical Faculty at Istanbul, as well as apparently healthy hospital workers were studied using a standardised questionnaire. BS patients were asked whether they experienced increased skin-mucosa lesions during the menstrual period. A similar questionnaire assessing this time the frequency of abdominal pain, chest pain and fever attacks was given to the patients with FMF. The healthy controls received both questionnaires. A total of 200 BS patients, 240 FMF patients and 250 healthy controls were studied. The most commonly reported symptom among both BS patients (51%) and healthy controls (62%) was the acneiform lesion. At least 79% patients with FMF reported attacks with menstruation, notably abdominal pain which, majority thought, could be differentiated from dysmenorrhea. Additionally, 76% of healthy controls reported having abdominal pain consistent most probably with dysmenorrhea. This survey showed that, in 68% of the patients with BS at least one skin mucosa lesion was exacerbated with menstruation, this was most commonly acneiform lesion. Menstruation had a slightly stronger effect on FMF, triggering at least one symptom in 79%. The main limitation of the study was the self-reported assessment methodology.

Migraine Management During Menstruation and Menopause.

Science.gov (United States)

MacGregor, E Anne

2015-08-01

Migraine is most prevalent in women during their reproductive years. An understanding of the effects of menstruation and menopause on migraine can enable neurologists to provide targeted and appropriate medical and hormonal strategies, enabling their patients to achieve better control of migraine and reduced disability. This article reviews the effects of hormonal events on migraine and summarizes the evidence-based options available for management. Estrogen "withdrawal" during the late luteal phase of the natural menstrual cycle and the hormone-free interval of combined hormonal contraceptives has long been implicated in the pathophysiology of menstrual migraine. However, more recent research suggests that other independent mechanisms may be relevant. Prostaglandin inhibitors used for management of dysmenorrhea are effective for associated menstrual migraine, suggesting a common pathophysiology. The interplay between serotonin and estrogen also deserves further research. Menstrual and perimenopausal migraine can be managed effectively using a variety of strategies, the choice of which depends on the efficacy of acute treatment, predictability and regularity of menstruation, use of contraception, and presence of menstrual disorders or perimenopausal vasomotor symptoms.

[Artificial cycle therapy of acupuncture and moxibustion for irregular menstruation].

Science.gov (United States)

Wu, Jie; Yang, Lijie; Chen, Yajie; Li, Qing; Chen, Lin

2015-03-01

Through the discussion on TCM physiological characters of females in follicular, ovulatory, luteal and menstrual phases and treatment principles, the clinical application of artificial cycle therapy of acupuncture and moxibustion was introduced for irregular menstruation and the typical cases were attached. It is suggested that the menstrual cycle follows the growth-consumption rule of yin, yang, qi and blood. The corresponding treatment principles should be applied in accordance with the change rule of menstrual cycle. Hence, it is worth to adopt the artificial cycle therapy of acupuncture and moxibustion for irregular menstruation in clinical application.

Recovery of menstruation after long-term chemotherapy and endocrine therapy in pre-menopausal patients with breast cancer.

Science.gov (United States)

Sakurai, Kenichi; Enomoto, Katsuhisa; Amano, Sadao

2011-04-01

A luteinizing hormone-releasing hormone (LH-RH) agonist and tamoxifen (TAM) are used in hormonal therapy following pre- and post-operative chemotherapy in pre-menopausal advanced breast cancer patients who are positive for hormone receptors. However, it remains to be clarified how often patients recover menstruation after long-term LH-RH agonist plus TAM therapy. In this study, the incidence of menstruation recovery after therapy was examined. The subjects included 125 pre-menopausal patients with breast cancer who were positive for hormone receptors and had undergone surgery at our institution. They were treated with four cycles of the CEF regimen and four cycles of docetaxel (Doc) before surgery as adjuvant chemotherapy. Thereafter, they were treated with an LH-RH agonist plus TAM for 24 months and followed to determine menstruation recovery. Menstruation resumed in 24 cases (19.2%) after the last LH-RH agonist treatment session. It took 7.3 ± 2.8 months for the patients to recover menstruation. The rate of menstruation recovery was 42.1% in patients aged 40 or younger and 9.2% in those aged 41 or older; the difference was significant. The period until menstruation recovery tended to be longer in older patients at the end of treatment. The menstruation recovery rate after therapy was higher in younger women. However, since ovarian function may be lost even in younger patients, the potential consequences of this therapy should be fully explained beforehand to patients who may wish to become pregnant.

Menstrual-Cycle and Menstruation Disorders in Episodic vs Chronic Migraine: An Exploratory Study.

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Spierings, Egilius L H; Padamsee, Aliya

2015-07-01

Migraine is a chronic condition of recurring moderate-to-severe headaches that affects an estimated 6% of men and 18% of women. The highest prevalence is in those 18-49 years of age, generally when women menstruate. It is divided into episodic and chronic migraine depending on the total number of headache days per month being 14 or less or 15 or more, respectively. Migraine has been associated with menorrhagia, dysmenorrhea, and endometriosis, the latter particularly in chronic migraine. We conducted a questionnaire survey of 96 women with migraine, 18-45 years old, to determine the occurrence of the menstrual-cycle disorders, oligomenorrhea, polymenorrhea, and irregular cycle, and the menstruation disorders, dysmenorrhea and menorrhagia, in episodic vs chronic migraine. The prevalence of menstrual-cycle disorders in general (41.2 vs 22.2%) and dysmenorrhea (51.0 vs 28.9%) was statistically significantly higher in the women with chronic migraine than in those with episodic migraine (P ≤ 0.05) (not corrected for multiple comparisons). Whether the migraine was menstruation sensitive, that is, the headaches consistently occurred or worsened with menstruation, did not impact the prevalence of menstrual disorders. We conclude that chronic migraine is possibly more often than episodic migraine associated with menstrual-cycle disorders in general and dysmenorrhea, without impact on menstruation sensitivity of the headaches. Wiley Periodicals, Inc.

Pubescent male students' attitudes towards menstruation in Taiwan: implications for reproductive health education and school nursing practice.

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Chang, Yu-Ting; Hayter, Mark; Lin, Mei-Ling

2012-02-01

To explore male students' attitudes towards menstruation. Menstruation is a biological event that is often surrounded by secrecy and social stigma that causes anxiety amongst many young girls. A key element of this is the attitudes of young males towards this reproductive health issue. However, the literature around what young males think and feel about menstruation is limited. Qualitative. A sample of 27 male students aged between 10-12 years participated in five focus groups. Data were then subject to a thematic analysis. Five themes emerged from the data analysis that reflected the boys' feelings, experiences and attitudes towards menstruation: 'A silent topic', 'An unimportant issue', 'Errant information about menstruation'. In addition, according to their experience, participants gradually came to see menstruation from the 'menstrual stereotype' viewpoint. In their social life, they made choices that resulted in gradually regulating their behaviour that affected their 'relationships with girls'. Young boys have misguided knowledge about menstruation and this helps to perpetuate the stigma surrounding this element of reproductive health. Boys also express a desire to learn more but are often restricted in this by home and school. School nurses are the best placed professionals to address this issue. Menstrual education with boys should take a greater prominence than it often does in sexual health education in schools. Such inclusion will provide boys with a balanced and accurate knowledge base and therefore help towards reducing the social stigma around menstruation that is often experienced by young girls. © 2011 Blackwell Publishing Ltd.

Sociocultural attitudes surrounding menstruation and alternative menstrual products: the explanatory role of self-objectification.

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Grose, Rose Grace; Grabe, Shelly

2014-01-01

We extend objectification theory research to consider the relationship between self-objectification and attitudes toward an alternative menstrual product in a diverse sample of female undergraduates from the United States (N = 151). We use a survey design to investigate attitudes toward one's menstruation as a potential mechanism that may explain this relationship. Reactions to an alternative menstrual product were predominantly negative, supporting prior research on stigma and shame surrounding menstruation. Exploratory structural equation modeling revealed attitudes toward one's menstruation mediated the relationship between self-objectification and participants' reactions to an alternative menstrual product. Implications for women's health are discussed.

Adolescence, Advertising, and the Ideology of Menstruation.

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Merskin, Debra

1999-01-01

Conducted a content analysis of 10 years of feminine hygiene advertisements in "Seventeen" and "Teen" magazines. Finds that advertising copy in these magazines works to dispel myths about menstruation but that few black models are shown. Discusses advertising as an element of socialization for adolescent girls. (SLD)

The effect of menstruation on psychiatric hospitalization.

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Weston, Jaclyn; Speroni, Karen Gabel; Ellis, Terri; Daniel, Marlon G

2012-07-01

This study evaluated the effect of menstruation on psychiatric hospitalization. We conducted a retrospective chart review of the medical records of 177 women who met the eligibility criteria. Data collected included demographic details, primary and secondary diagnoses, date of last menstrual period (LMP), medication adherence, psychiatric hospitalization length of stay, previous psychiatric admissions (including those related to menstruation), discharge referrals, and readmissions. The majority of women were admitted for major depression, were single, Caucasian, and had a mean age of 34. A disproportionate percentage (37%) of women had their LMP within 5 days of psychiatric hospitalization (p = 0.0006). The overall average length of stay was 4.37 days, and 48.3% had a previous psychiatric admission. Medication adherence was routinely not documented (77.4%). Psychiatric hospitalizations for women are significantly greater within 5 days of their LMP. Nursing education and improved documentation are warranted to decrease the potential for readmission. Copyright 2012, SLACK Incorporated.

Menstruation, menstrual protection and menstrual cycle problems. The knowledge, attitudes and practices of young Australian women.

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Abraham, S; Fraser, I; Gebski, V; Knight, C; Llewellyn-Jones, D; Mira, M; McNeil, D

1985-02-18

The results of a survey of 1377 young Australian women aged 14 to 19 years, conducted to determine their attitudes, state of knowledge and practices with regard to menstruation, are presented. The young women, as a group, lacked sufficient information about menstruation, about the time of ovulation, about menstrual discharge, and about the use of tampons. A high proportion (80%) considered menstruation to be inconvenient or embarrassing. Certain measures aimed at remedial action are suggested.

Mexican adolescents' experience of menarche and attitudes toward menstruation: role of communication between mothers and daughters.

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Marván, M L; Molina-Abolnik, M

2012-12-01

First, to explore the kind of information that Mexican mothers give their daughters about menstruation before their menarche, and to study the impact of this communication on how prepared the daughters felt when they experienced their menarche. Second, to investigate the influence of the menarcheal experience on attitudes toward menstruation. Cross-sectional survey. Sample of adolescents attending 3 different public schools. 405 Mexican postmenarcheal adolescents, aged 12-15 years. Participants answered a questionnaire that had 3 parts: (a) General data, (b) topics related to menses that participants had discussed with their mothers prior to menarche, and (c) menarcheal experience. They also answered a questionnaire about menstrual attitudes. Although most of the participants knew what they should do when they experienced their menarche, only 39% stated they had felt prepared to start menstruating. Regarding menstrual attitudes, adolescents scored highest on Negative Feelings and Secrecy rather than on Positive Feelings. Participants who had previously discussed the emotional aspects of menses with their mothers were more likely to claim they had felt prepared to start menstruating when they got their first period (OR = 3.45). The fact that adolescents felt prepared to start menstruating predicted positive attitudes toward menstruation (β = .19) Discussing the emotional aspects of menses prior to menarche is crucial to being prepared for menarche, and to holding positive attitudes toward menstruation. Information on biological knowledge and practical aspects of menses needs to be supplemented with emotional issues. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Doing Harm in the Name of Protection: Menstruation as a Topic for Sex Education.

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Diorio, Joseph A.; Munro, Jennifer A.

2000-01-01

Pubertal changes in girls and boys are treated differently in New Zealand schools. Girls learn about menstruation in a scientific, bleak manner, getting an unrealistic picture of growing up. Boys receive positive information about exciting, powerful bodily changes. By protecting girls from problems associated with menstruation, schools risk…

Relation of supplementary feeding to resumptions of menstruation and ovulation in lactating postpartum women.

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Li, Wei; Qiu, Yi

2007-05-20

Resumption of menstrual cycles is one of the indicators for restoration of reproductive capability in postpartum women. However, menstruation does not necessarily mean that ovulation has taken place. The aim of this study was to investigate the relation of supplementary feeding to return of menstruation and ovulation after delivery. A questionnaire was used to obtain data from 101 breastfeeding mothers. The following elements were analyzed: age, education level, breastfeeding practice, time of return of menstruation, contraceptive practice, and starting time of supplementary feeding during the lactation at intervals of 6 weeks to 18 months after delivery. The ovulation was continuously monitored by ultrasonography and basal body temperature (BBT) measurement. By ultrasonography, 53 of the 101 women (52.5%) had the first ovulation (follicle > 1.8 cm in diameter) within 154 days after delivery on average, among whom 11 (10.9%, 11/101) had restoration of ovulation within 4 months and 42 (41.6%, 42/101) had it after 4 months. In women with follicles > 1.8 cm in diameter (n = 53), the menstruation resumed (138 +/- 84) days after delivery, and the supplementary feeding was started at (4.0 +/- 1.1) months, which were significantly earlier than those in the women with follicular diameter menstruation before the end of ultrasonographic monitoring, while only 8 in the women with follicular diameter menstruation (n = 100, r = 0.4764, P < 0.01) and first ovulation after delivery (n = 53, r = 0.5554, P < 0.01). In this series, no woman had pregnancy within 18 months postpartum. Supplementary feeding can affect the restoration of menstrual cycles and ovulation in lactating postpartum women.

Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

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Sakurai, Kenichi; Matsuo, Sadanori; Enomoto, Katsuhisa; Amano, Sadao; Shiono, Motomi

2011-01-01

Little is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy. The subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined. Menstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment. This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

Knowledge and practices regarding menstruation among adolescent girls in an urban slum, Bijapur.

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Udgiri, Rekha; Angadi, M M; Patil, Shailaja; Sorganvi, Vijaya

2010-08-01

Adolescence is a crucial period in woman's life. The adolescent girls of today are the mothers of tomorrow in whose hand lie the future of her family, community and the nation. Because of the scarcity of information regarding the problems of adolescent girls, particularly in urban areas, the present study was undertaken to elicit information about the knowledge and practices regarding menstruation among adolescent girls. With this objective, a community-based cross-sectional study was done in an urban field practice area of BLDEA's Shri BM Patil Medical College, Bijapur. The study subjects included all adolescent girls who had attained menarche. Data was collected by questionnaire method and analysed. Out of 342 adolescent girls 324 (94.74%) were literate. Only 63 (18.42%) had knowledge about menstruation prior to attainment of menarche and this association was found to be statistically significant. The main source of information about menstruation was mother ie, 195 (57.01%). Nearly 81.58% adolescent girls were lacking knowledge about menstruation prior to menarche, this reflects upon the standard of awareness in the society to such important event and it also leads to negative reaction to menarche.

More than Just a Punctuation Mark: How Boys and Young Men Learn about Menstruation

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Allen, Katherine R.; Kaestle, Christine E.; Goldberg, Abbie E.

2011-01-01

Parents, peers, schools, and the media are the primary contexts for educating young people about sexuality. Yet girls receive more sex education than boys, particularly in terms of menstruation. Lack of attention to how and what boys learn about menstruation has consequences for their private understanding about the biology of reproduction and…

Use of Oral Contraceptives to Manipulate Menstruation in Young, Physically Active Women.

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Schaumberg, Mia A; Emmerton, Lynne M; Jenkins, David G; Burton, Nicola W; Janse de Jonge, Xanne A K; Skinner, Tina L

2018-01-01

Menstruation and menstrual symptoms are commonly cited barriers to physical activity in women. The delay or avoidance of menstruation through extended oral-contraceptive (OC) regimens may mitigate these barriers, yet information on menstrual-manipulation practices in young physically active women is sparse. The objective of this study was to investigate prevalence of, and reasons for, menstrual manipulation with OCs in recreationally and competitively active women. One hundred ninety-one recreationally active (self-reported moderate to vigorous physical activity 150-300 min/wk) women (age 23 ± 5 y), 160 subelite recreationally active (self-reported moderate to vigorous physical activity >300 min/wk) women (age 23 ± 5 y), and 108 competitive (state-, national- or international-level) female athletes (age 23 ± 4 y) completed a self-administered questionnaire assessing OC-regimen habits and reasons for manipulation of menstruation. The majority (74%) of OC users reported having deliberately manipulated menstruation at least once during the previous year, with 29% reporting having done so at least 4 times. Prevalence of menstrual manipulation (at least once in the previous year) was not different between competitive athletes, subelite recreationally active women, and recreationally active women (77% vs 74% vs 72%; P > .05). The most cited reasons for manipulating menstruation were special events or holidays (rated by 75% as important/very important), convenience (54%), and sport competition (54%). Menstrual manipulation through extended OC regimens is common practice in recreationally and competitively active young women, for a range of reasons relating to convenience that are not limited to physical activity. This strategy may help reduce hormone-related barriers to exercise participation, thereby positively affecting participation and performance.

Knowledge and awareness regarding menstruation and HIV/AIDS among schoolgoing adolescent girls.

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Jain, Rakhi; Anand, Puneet; Dhyani, Anuj; Bansal, Deshant

2017-01-01

Menstruation in our country is associated with various myths and restrictions leading to lack of awareness among adolescent girls. Insufficient menstrual hygiene practices are the cause of stress associated with menstruation and reproductive tract infections. Sexually transmitted infections and HIV/AIDS are not openly discussed in our society making adolescents vulnerable to them. To assess the knowledge of school going adolescent girls regarding menstrual hygiene and HIV/AIDS. Girls studying in class 8 th -12 th standard and who have attained menarche were included in the study. A predesigned questionnaire, which consisted of questions related to menstrual awareness and knowledge about HIV/AIDS was used for data collection. Data was analysed using SPSS software and results were interpreted into percentages. 282 girls took part in the study. Mean age of girls was 14.70 ± 1.5 years. Median age of girls was 15 years. Knowledge regarding menstrual hygiene and HIV/AIDS was found to be only satisfactory leaving a scope of improvement. Mother was the main source of information regarding both menstruation and HIV/AIDS. A comprehensive health education programme involving mothers is required to remove various misconceptions and taboos associated with menstruation and make it a pleasant experience for adolescent girls. Information, education and awareness programmes need to be strengthened to spread awareness regarding HIV/AIDS.

Knowledge and awareness regarding menstruation and HIV/AIDS among schoolgoing adolescent girls

Directory of Open Access Journals (Sweden)

Rakhi Jain

2017-01-01

Full Text Available Introduction: Menstruation in our country is associated with various myths and restrictions leading to lack of awareness among adolescent girls. Insufficient menstrual hygiene practices are the cause of stress associated with menstruation and reproductive tract infections. Sexually transmitted infections and HIV/AIDS are not openly discussed in our society making adolescents vulnerable to them. Aim: To assess the knowledge of school going adolescent girls regarding menstrual hygiene and HIV/AIDS. Materials and Methods: Girls studying in class 8th-12th standard and who have attained menarche were included in the study. A predesigned questionnaire, which consisted of questions related to menstrual awareness and knowledge about HIV/AIDS was used for data collection. Data was analysed using SPSS software and results were interpreted into percentages. Results: 282 girls took part in the study. Mean age of girls was 14.70 ± 1.5 years. Median age of girls was 15 years. Knowledge regarding menstrual hygiene and HIV/AIDS was found to be only satisfactory leaving a scope of improvement. Mother was the main source of information regarding both menstruation and HIV/AIDS. Conclusion: A comprehensive health education programme involving mothers is required to remove various misconceptions and taboos associated with menstruation and make it a pleasant experience for adolescent girls. Information, education and awareness programmes need to be strengthened to spread awareness regarding HIV/AIDS.

SOCIAL ASPECTS OF MENSTRUATION RELATED PRACTICES IN ADOLESCENT GIRLS OF DISTRICT DEHRADUN

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Ruchi Juyal

2013-09-01

Full Text Available Context: Menstrual hygiene is an issue that every girl and woman has to deal with in her life, but there is lack of awareness on the process of menstruation. The taboos surrounding this issue in the society prevent girls and women from articulating their menstrual needs. It is now becoming increasingly recognized that the social and cultural significance of menstruation interacts with the physiological process to produce culturally determined norms and practices. Settings and Design: Cross-Sectional conducted in two randomly selected Inter colleges (one rural and one urban of district Dehradun of Uttarakhand state.Methods and Material: 453 girls studying in 9th to 12th grades were interviewed by using a prestructured and pretested questionnaire regarding various aspects of menstruation process.Statistical analysis used: percentages and Chi-square testResults: Most of the girls faced one or the other kind of social and / or religious restriction during their menstrual periods. Maximum restriction was observed in going to the temple (87.4 % followed by prohibition in touching pickles (48.6 %. These restrictions were equally reported by the urban and rural girls.Conclusions: Girls should be made aware regarding physiological basis of menstruation and a change in beliefs and attitudes need to be attained to ensure optimal behaviour and thereby prompting of a healthy menstrual life styles and practices.

[Rehabilitation following interruption of pregnancy since the legalization of abortion. I. Structure of patients, duration of disability, menstruation and effects of contraceptive counseling].

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Zwahr, C; Knorre, P; Kunz, L

1974-01-04

Rehabilitation after abortion is an important consideration for fertile women and is defined here as recovery of the physical, psychic, and social condition that had been present prior to abortion. 206 women were studied 6-12 months after induced abortion (before 12 weeks by the vacuum suction apparatus method). 9.2% of the women attributed worsening of their physical condition to recent abortion. Duration of work incapacity was 8-21 days, with an average of 19 days; younger women and women with fewer children recuperated more quickly. In most cases menstruation returned late, an average of 35 days after the last period. 33% of the menstruations were unusually heavy. Duration of menstruation decreased from an average of 6.5 days for the 1st period to an average of 5.4 days by the 6th, women over 30 became regular more quickly than younger women. The study revealed that 33% of the women did not use contraceptives even after abortion. After intensive counseling, a disappointing 22.9% still resisted using contraceptives.

An Exploration of Issues around Menstruation for Women with Down Syndrome and Their Carers

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Mason, Linda; Cunningham, Cliff

2008-01-01

Background: There is little research on issues related to menstruation for women with Down syndrome, yet they may experience menstruation in a qualitatively different way from normal women, which impacts on their quality of life and that of their families and carers. The aim of this qualitative study was to explore issues with the women and/or…

Young Japanese college students with dysmenorrhea have high frequency of irregular menstruation and premenstrual symptoms.

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Fujiwara, Tomoko; Nakata, Rieko

2007-01-01

In this study, to estimate the current status of young women with menstrual disorders, the relation among dysmenorrhea, irregular menstruation and premenstrual symptoms was investigated by a questionnaire. Subjects ranging from 18 to 20 years old were recruited from 522 female students at Ashiya College in Japan. The intensity of dysmenorrhea was classified into 3 grades (score 1, not requiring analgesic; score 2, painful, requiring analgesic; score 3, painful, not relieved by analgesic). All participants were further divided into subsequent groups as having premenstrual symptoms or not and those having regular or irregular menstruation. Dysmenorrhea scores in the students with premenstrual symptoms or irregular menstruation were significantly higher than those without these symptoms (1.66+/-0.66 vs 1.41+/-0.59; 1.62+/-0.68 vs 1.49+/-0.61, respectively). There was no significant relation in the incidence between premenstrual symptoms and irregular menstruation. These findings suggest that considerable numbers of young women with dysmenorrhea are associated with premenstrual symptoms.

A cross-sectional study of the beliefs and attitudes towards menstruation of Chinese undergraduate males and females in Hong Kong.

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Wong, Wing Chi; Li, Mei Kuen; Chan, Wai Ying Veronica; Choi, Yuen Yu; Fong, Chi Hung Sandra; Lam, Ka Wah Kara; Sham, Wun Chi; So, Ping Ping; Wong, Kit; Yeung, Kuen Ha; Yeung, Tsz Yan

2013-12-01

To explore the beliefs and attitudes towards menstruation of Chinese undergraduates in Hong Kong and to compare those of (1) male and female undergraduates with those of (2) undergraduates studying health-related vs. nonhealth-related programmes. Menstruation is typically viewed as a forbidden topic or a troublesome experience. These negative beliefs and attitudes result from existing myths and taboos associated with cultural factors and health education levels. A cross-sectional survey was conducted in all universities in Hong Kong. Undergraduates were invited through convenience sampling to complete a questionnaire assessing their attitudes and beliefs towards menstruation. A questionnaire on 'beliefs about and attitudes towards menstruation' was adopted. Questionnaires were self-administered by the respondents. A total of 450 questionnaires were distributed, and a response rate of 96.6% was obtained; 416 completed questionnaires were collected and analysed. Many Chinese undergraduates agreed that menstruation is annoying, causes disability, involves prescription and proscription and is not pleasant. When comparing the beliefs and attitudes towards menstruation of Chinese male undergraduates with those of female undergraduates, females tended to disagree that menstruation should be maintained secret, but tended to agree that it was annoying. When comparing the beliefs and attitudes towards menstruation of Chinese undergraduates studying health-related programmes with those under nonhealth-related programmes, the latter group exhibited a higher level of belief in prescription and proscription for menstruation than the former group. Chinese undergraduates in Hong Kong were influenced by the traditional Chinese culture and social environment, resulting in negative attitudes towards menstruation. This study recommends that sex education, especially reproductive health education, be extended to tertiary education. This study provides relevant information on planning

Becoming a Woman: Considerations in Educating Adolescents about Menstruation. Revised 1988. Working Paper No. 169.

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Stubbs, Margaret L.; And Others

This paper reports findings that have emerged from several studies conducted concerning young girls' and boys' attitudes toward menstruation. The research work discussed included: (1) cross-sectional data about menarcheal experience and about attitudes toward menstruation from early adolescent girls in grades six through nine; (2) cross-sectional…

[Successful surgical treatment for catamenial pneumothorax at the time of menstruation].

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Kita, Hidefumi; Shiraishi, Yuji; Katsuragi, Naoya; Shimoda, Kiyomi; Saitou, Miyako

2013-11-01

A 39-year-old female was referred to our hospital due to repeated right pneumothorax. Each episode was related to the onset of menstruation, suggesting catamenial pneumothorax. Thoracoscopy showed multiple blue berry spots on the diaphragm. Partial resection of the diaphragm including these lesions were performed. But she had a recurrent right pneumothorax. Treatment with a gonadotropin-releasing hormone analogue was started, resulting in failure to introduce menopose and the pneumothorax repeatedly appeared again. Reoperation was intentionally done at the time of menstruation enable to find the lesion. Patient is free from pneumothorax more than 6 years after surgery.

Improving pre- and postmenarcheal 12-year-old girls' attitudes toward menstruation.

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Rembeck, Gun I; Gunnarsson, Ronny K

2004-08-01

Adolescence is a time of rapid changes, including risk for unwanted pregnancies and sexually transmitted infections. Education may improve understanding and attitudes toward menstruation among adolescents thus increasing their awareness of risks and enabling them to protect themselves accordingly. To investigate effects of education on attitudes, two interventions were compared in 345 12-year-old girls. The new, active intervention given to premenarcheal girls just before menarche resulted in improvements in attitudes toward menstruation compared with standard intervention. Thus, just before menarche girls should be offered education modeled after the active intervention. The education must be concrete and based on multisensory learning.

Teaching More than the Facts of Menstruation: Exercises to Stimulate Dialogue about a Taboo Subject.

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Taylor, Christina J.

1981-01-01

Presents nine exercises designed to help students and teachers become more aware of their attitudes about menstruation and to move beyond the realms of mystery, ignorance, and taboos. Participants list and analyze expressions used to refer to menstruation, discuss pleasant and unpleasant experiences, and recall feelings on first learning of…

Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.

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Sasamoto, Naoko; Ueda, Yutaka; Amemiya, Kyoka; Enomoto, Takayuki; Morii, Eiichi; Adachi, Kazushige

2014-01-01

Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy. The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

Premenstrual syndrome and attitudes toward menstruation in a sample of nursing students.

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Guvenc, Gulten; Kilic, Ayse; Akyuz, Aygul; Ustunsoz, Ayfer

2012-09-01

The aim of this study was to evaluate baccalaureate nursing students' attitudes toward menstruation, and to analyze the frequency of premenstrual syndrome (PMS) symptoms, as well as the relationship between attitudes toward menstruation and PMS symptoms. This cross-sectional study was carried out between February 15 and March 10, 2009, in Ankara Turkey. The study participants were 250 undergraduate nursing student volunteers. Data were collected using a demographic questionnaire, the validated Turkish version of the Menstrual Attitude Questionnaire (MAQ), and the validated Turkish Premenstrual Syndrome (PMS) Scale. Obtained data were analyzed using SPSS version 15.0. The average age of participants was 19.89 ± 1.43. The MAQ's five subscales' mean scores ranged from 2.67 ± 0.58 to 3.37 ± 0.52, indicating natural to moderate attitudes toward menstruation. The mean PMS score was 114.86 ± 35.15, indicating moderate PMS symptoms. PMS symptoms were detected in 36.4% of the nursing students. Thirty one percent of the students reported having dysmenorrhoea during every menstrual cycle. Students who had PMS symptoms scored significantly higher on the debilitation subscale and scored significantly lower on the denial subscale of the MAQ (p menstruation was considered to be a natural event by most of the nursing students. In addition, dysmenorrhea was found to be the most common menstrual problem and the rate of PMS was found lower than that found in previous researches conducted in Turkey.

Clinical significance of neonatal menstruation.

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Brosens, Ivo; Benagiano, Giuseppe

2016-01-01

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cultural perceptions and practices around menarche and adolescent menstruation in the United States.

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Stubbs, Margaret L

2008-01-01

This overview details the persistence of negative characterizations of the menstrual cycle as a feature of the current cultural context in which girls begin menstrual life in the United States. In addition, research on girls' current menstrual attitudes and experiences within this context are reviewed. Current research suggests that girls are not very knowledgeable about menstruation, and that menstrual education continues to provide girls with mixed messages, such as: menstruation is a normal, natural event, but it should be hidden. Girls' attitudes and expectations about menstruation are negatively biased and have been found to contribute to self-objectification, body shame, and lack of agency in sexual decision-making. Although preparation has been found to be associated with more positive menarcheal and menstrual experiences, specificity about what constitutes "good" preparation has not been well articulated. Implications for promoting the menstrual cycle among young girls as a vital sign in service of monitoring their health are discussed.

Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes.

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Wong, M; O'Neill, S; Walsh, G; Smith, I E

2013-01-01

Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex®), used with chemotherapy to preserve ovarian function and maintain fertility. Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses. About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n=30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries. The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.

Menstruation in Rural Igbo Women of South East Nigeria: Attitudes ...

African Journals Online (AJOL)

Menstruation in Rural Igbo Women of South East Nigeria: Attitudes, Beliefs and Practices. ... African Journal of Reproductive Health ... Some respondents observed self-imposed restrictions on exercises, food items, visits and sex in order to ...

Does Menstruation Explain Gender Gaps in Work Absenteeism?

Science.gov (United States)

Herrmann, Mariesa A.; Rockoff, Jonah E.

2012-01-01

Ichino and Moretti (2009) find that menstruation may contribute to gender gaps in absenteeism and earnings, based on evidence that absences of young female Italian bank employees follow a 28-day cycle. We find this evidence is not robust to the correction of coding errors or small changes in specification, and we find no evidence of increased…

Determinants of pre-menarcheal knowledge of menstruation and sociocultural implications in college going girls: A community-based cross-sectional study from Latur, Maharashtra

Directory of Open Access Journals (Sweden)

Namrata Arvind Thakur

2016-01-01

Full Text Available Introduction: Adolescence marks the onset of female puberty. The first menstruation is often horrifying and traumatic to an adolescent girl because it usually occurs without her knowing about it. Implications of a girl′s response to menarche have a socio-cultural and religious significance. Aim and Objective: To study the sociocultural and physiological implications of menstruation in college going girls. Materials and Methods: This was a community-based cross-sectional observational study undertaken among college girls. All the girls (n = 252 of the college were enrolled in the study. A structured questionnaire was used as the study tool. The questionnaire included topics related to sociodemographic information, sociocultural implications and first informant about the physiological process of menstruation along with its timing. Results: Majority of the study subjects (77.40% observed restrictions for religious/holy things. Sleep disturbances were the most common (59% disturbance faced by the study subjects. Of a total of 252 respondents, majority [104 (41.30%] had leg cramps. The first informant of menstruation was the mother in 196 (77.78% girls. Of 252 girls, 86 (34.12% had pre-menarcheal knowledge of menstruation. Mothers from the urban area and with better education tend to give knowledge of menstruation prior to menarche of her daughter. An increasing trend was observed with increasing educational status of the mother and proportion of them giving pre-menarcheal knowledge of menstruation to their daughter. Conclusions: Menstruation is associated with a high burden of sociocultural implications. Pre-menarcheal knowledge of menstruation is poor. Mothers from the urban area and with better educational level tend to give knowledge of menstruation prior to menarche of their daughter.

Cultural interpretation of menstruation in relation to adolescent girls ...

African Journals Online (AJOL)

Information derived from researching cultural information on menstruation and other forms of blood flow in adolescent girls in Nigeria can contribute extensively to existing knowledge about the female world in general and on adolescent girls in particular. This will further encourage ongoing advocacy programmes in ...

Primary spontaneous pneumothorax in menstruating females has high recurrence

Science.gov (United States)

Mehta, Christopher K.; Stanifer, Bryan P.; Fore-Kosterski, Susan; Gillespie, Colin; Yeldandi, Anjana; Meyerson, Shari; Odell, David D.; DeCamp, Malcolm M.; Bharat, Ankit

2016-01-01

Background Primary spontaneous pneumothorax (PSP) is treated based on studies that have predominantly consisted of tall male subjects. Here we determined recurrence of PSP in average-statured menstruating women and studied prevalence of catamenial pneumothorax (CP) in this population. Methods Males and menstruating females, aged 18-55 years, without underlying lung disease or substance abuse were retrospectively studied between 2009-2015. A chest pathologist reviewed all specimens for thoracic endometriosis. Kaplan-Meier curves were constructed to determine recurrence. Results The median age of females (n=33) and males (n=183) was 33.4 and 31.6 years, respectively. In females, nine (27%) had left-sided and 24 (73%) had right-sided PSP, treated with tube thoracostomy. Recurrence occurred in 21 (64%) females with median follow up of 14 months and was treated with thoracoscopic pleurodesis. Right PSP had higher recurrence (70%) compared to left (56%, p=0.02). Four females (12%) presented with recurrent tension pneumothorax within six months. Eight (24%) patients had PSP within 72 hours of menses, meeting clinical criteria of CP. All these were placed on hormonal suppression after initial episode but went on to develop recurrence that was treated with pleurodesis. However, classic endometrial glands were not found in any biopsy specimens obtained during the thoracoscopy. In contrast to female subjects, only 8 (4.4%) average-statured males had recurrence (p<0.001) with a median follow up of 16 months. Conclusions PSP in healthy average-statured menstruating women has high recurrence compared to male counterparts. CP is a clinical diagnosis and often recurs despite hormonal suppression therapy. PMID:27345097

Significance and nature of bystander responses induced by various agents.

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Verma, Neha; Tiku, Ashu Bhan

2017-07-01

Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

Associations of Age, BMI, and Years of Menstruation with Proximal Femur Strength in Chinese Postmenopausal Women: A Cross-Sectional Study.

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Kang, Huili; Chen, Yu-Ming; Han, Guiyuan; Huang, Hua; Chen, Wei-Qing; Wang, Xidan; Zhu, Ying-Ying; Xiao, Su-Mei

2016-01-23

This study aimed to elucidate the associations of age, BMI, and years of menstruation with proximal femur strength in Chinese postmenopausal women, which may improve the prediction of hip fracture risk. A cross-sectional study was conducted in 1322 Chinese postmenopausal women recruited from communities. DXA images were used to generate bone mineral density (BMD) and geometric parameters, including cross-sectional area (CSA), outer diameter (OD), cortical thickness (CT), section modulus (SM), buckling ratio (BR) at the narrow neck (NN), intertrochanter (IT), and femoral shaft (FS). Relationships of age, BMI, and years of menstruation with bone phenotypes were analyzed with the adjustment of height, age at menarche, total daily physical activity, education, smoking status, calcium tablet intake, etc. Age was associated with lower BMD, CSA, CT, SM, and higher BR (p menstruation had the positive relationships with proximal femur strength (p menstruation were 0.14%-1.34%, 0.20%-2.70%, and 0.16%-0.98%, respectively. These results supported that bone strength deteriorated with aging and enhanced with higher BMI and longer time of years of menstruation in Chinese postmenopausal women.

Primary Spontaneous Pneumothorax in Menstruating Women Has High Recurrence.

Science.gov (United States)

Mehta, Christopher K; Stanifer, Bryan P; Fore-Kosterski, Susan; Gillespie, Colin; Yeldandi, Anjana; Meyerson, Shari; Odell, David D; DeCamp, Malcolm M; Bharat, Ankit

2016-10-01

Primary spontaneous pneumothorax (PSP) is treated on the basis of studies that have predominantly consisted of tall male subjects. Here, we determined recurrence of PSP in average-statured menstruating women and studied prevalence of catamenial pneumothorax (CP) in this population. Men and menstruating women, aged 18 to 55 years, without underlying lung disease or substance abuse were retrospectively studied between 2009 and 2015. A chest pathologist reviewed all specimens for thoracic endometriosis. Kaplan-Meier curves were constructed to determine recurrence. The median age of women (n = 33) and men (n = 183) was 33.4 and 31.6 years, respectively. In women, 9 (27%) had left-sided and 24 (73%) had right-sided PSP, treated with tube thoracostomy. Recurrence occurred in 21 women (64%) with median follow-up of 14 months, and they were treated with thoracoscopic pleurodesis. Right PSP had higher recurrence (70%) than left PSP (56%, p = 0.02). Four women (12%) presented with recurrent tension pneumothorax within 6 months. Eight patients (24%) had PSP within 72 hours of menses, meeting clinical criteria of CP. All these were placed on hormonal suppression after initial episode but went on to experience recurrence that was treated with pleurodesis. Classical endometrial glands were not found in any biopsy specimens obtained during the thoracoscopy. In contrast to female subjects, only 8 average-statured men (4.4%) had recurrence (p < 0.001) with a median follow-up of 16 months. PSP in healthy average-statured menstruating women has high recurrence compared with male counterparts. CP is a clinical diagnosis and often recurs despite hormonal suppression therapy. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Imagery Associated with Menstruation in Advertising Targeted to Adolescent Women.

Science.gov (United States)

Havens, Beverly; Swenson, Ingrid

1988-01-01

Analyzed imagery in advertisements in "Seventeen" magazine for sanitary products and products for relief of menstrual symptoms, looking for recurrent themes in text, context, and tone. Found menstruation depicted as a "hygienic crisis" best managed by an effective "security system" affording protection and "peace…

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

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Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

2015-02-01

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding.

Science.gov (United States)

Schatz, Frederick; Guzeloglu-Kayisli, Ozlem; Arlier, Sefa; Kayisli, Umit A; Lockwood, Charles J

2016-06-01

Human pregnancy requires robust hemostasis to prevent hemorrhage during extravillous trophoblast (EVT) invasion of the decidualized endometrium, modification of spiral arteries and post-partum processes. However, decidual hemorrhage (abruption) can occur throughout pregnancy from poorly transformed spiral arteries, causing fetal death or spontaneous preterm birth (PTB), or it can promote the aberrant placentation observed in intrauterine growth restriction (IUGR) and pre-eclampsia; all leading causes of perinatal or maternal morbidity and mortality. In non-fertile cycles, the decidua undergoes controlled menstrual bleeding. Abnormal uterine bleeding (AUB) accompanying progestin-only, long-acting, reversible contraception (pLARC) accounts for most discontinuations of these safe and highly effective agents, thereby contributing to unwanted pregnancies and abortion. The aim of this study was to investigate the role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. We conducted a critical review of the literature arising from PubMed searches up to December 2015, regarding in situ and in vitro expression and regulation of several specific proteins involved in uterine hemostasis in decidua and cycling endometrium. In addition, we discussed clinical and molecular mechanisms associated with pLARC-induced AUB and pregnancy complications with abruptions, chorioamnionitis or pre-eclampsia. Progestin-induced decidualization of estradiol-primed human endometrial stromal cells (HESCs) increases in vivo and in vitro expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) while inhibiting plasminogen activators (PAs), matrix metalloproteinases (MMPs), and the vasoconstrictor, endothelin-1 (ET-1). These changes in decidual cell-derived regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone prevent hemorrhage during EVT invasion and

Students' perceptions and doubts about menstruation in developing countries: a case study from India.

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Chothe, Vikas; Khubchandani, Jagdish; Seabert, Denise; Asalkar, Mahesh; Rakshe, Sarika; Firke, Arti; Midha, Inuka; Simmons, Robert

2014-05-01

Menstrual education is a vital aspect of adolescent health education. Culture, awareness, and socioeconomic status often exert profound influence on menstrual practices. However, health education programs for young women in developing countries do not often address menstrual hygiene, practices, and disorders. Developing culturally sensitive menstrual health education and hygiene programs for adolescent females has been recommended by professional health organizations like the World Health Organization and UNICEF. These programs cannot be developed without understanding existing myths and perceptions about menstruation in adolescent females of developing countries. Thus, the purpose of this qualitative study from India was to document existing misconceptions regarding menstruation and perceptions about menarche and various menstrual restrictions that have been understudied. Out of the 612 students invited to participate by asking questions, 381 girls participated by asking specific questions about menstruation (response rate = 62%). The respondents consisted of 84 girls from sixth grade, 117 from seventh grade, and 180 from eighth grade. The questions asked were arranged into the following subthemes: anatomy and physiology, menstrual symptoms, menstrual myths and taboos, health and beauty, menstrual abnormalities, seeking medical advice and home remedies; sanitary pads usage and disposal; diet and lifestyle; and sex education. Results of our study indicate that students had substantial doubts about menstruation and were influenced by societal myths and taboos in relation to menstrual practices. Parents, adolescent care providers, and policy makers in developing countries should advocate for comprehensive sexuality education and resources (e.g., low-cost sanitary pads and school facilities) to promote menstrual health and hygiene promotion.

Menstruation and School Absenteeism: Evidence from Rural Malawi

OpenAIRE

Grant, Monica J.; Lloyd, Cynthia B.; Mensch, Barbara S.

2013-01-01

The provision of toilets and menstrual supplies has emerged as a promising programmatic strategy to support adolescent girls’ school attendance and performance in less developed countries. We use the first round of the Malawi Schooling and Adolescent Survey (MSAS) to examine the individual- and school-level factors associated with menstruation-related school absenteeism. The MSAS is a school-based longitudinal survey of adolescent students enrolled in coed public primary schools in the southe...

Spanish women's attitudes towards menstruation and use of a continuous, daily use hormonal combined contraceptive regimen.

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Sánchez-Borrego, Rafael; García-Calvo, Carmen

2008-02-01

The main objective of this survey was to explore the attitude of Spanish women towards menstruation, as well as their acceptability of a daily, continuous, combination oral contraceptive regimen. National survey carried out in Spain in 2006. A total of 588 women aged between 18 and 45 years old answered an anonymous questionnaire that included questions regarding menstruation and acceptability of new contraceptive regimens. Overall, 24.5% of women expressed interest in using the continuous oral contraceptive regimen. This percentage increased up to nearly 50% in women younger than 25 years old and those not using any contraceptive method but willing to use them in the future. The attitude of Spanish women towards menstruation observed in this survey seems to be more conservative than that obtained in other recent international surveys. An improvement in the education provided by practitioners would help women to make informed decisions.

Menstruation across time: menarche, menstrual attitudes, experiences, and behaviors.

Science.gov (United States)

McPherson, Marianne E; Korfine, Lauren

2004-01-01

This study explored the relationship between early and current menstrual experiences. The primary hypothesis was that women who reported positive menarcheal experiences (including menstrual education and menarche) would tend to report positive current menstrual attitudes, experiences, and/or behaviors, and vice versa for women who reported negative menarcheal experiences. In this survey-based study, college-aged women (n = 327) were screened by completing a questionnaire concerning their menarcheal experiences. Women who had extremely negative ("negative group," n = 46) or extremely positive ("positive group," n = 38) early menstrual experiences returned to complete questionnaires concerning current menstrual attitudes, experiences, and behaviors. Early and current menstrual experiences were most strongly associated in the domain of menstrual attitudes. Women in the negative group reported more negative menstrual attitudes than did women in the positive group. There were additional associations between early menstrual experiences and measures of body image and health behaviors. Positive group participants reported more positive body image and better general health behaviors. Results suggest that early menstrual experiences may be related to menstrual experiences later in life. This study invites further investigation of the psychology of menstruation and suggests connecting menstruation with other women's health issues.

Teaching Taboo Topics: Menstruation, Menopause, and the Psychology of Women

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Chrisler, Joan C.

2013-01-01

The purpose of this article is (a) to consider reasons why women's reproductive processes receive so little attention in psychology courses and (b) to make an argument for why more attention is needed. Menstruation, menopause, and other reproductive events are important to the psychology of women. Reproductive processes make possible a social role…

Girls' equal participation in education. Period. : A field study on how Indian schoolgirls perceive menstruation stigmas to affect their access to education

OpenAIRE

Schylander, Hedvig

2017-01-01

Menstruation stigmas and a lack of facilities to manage periods have been identified as possible hinders for girls’ equal access to education all over of the world. This paper focuses on investigating how menstruation stigmas generate obstacles for girls’ equal access to, and participation in, education. Its aim is to investigate how girls in an Indian context perceive menstruation stigmas to affect them, particularly when it comes to school attendance and ability to learn in school. This is ...

Association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012

OpenAIRE

Mohamadirizi, Soheila; Kordi, Masoumeh

2013-01-01

Background: Menstruation signs are among the most common disorders in adolescents and are influenced by various environmental and psychosocial factors. This study aimed to define the association between menstruation signs and anxiety, depression, and stress in school girls in Mashhad in 2011-2012. Materials and Methods: This was a cross-sectional study on 407 high school girls in Mashhad who were selected through two-step random sampling. The students completed a questionnaire concerning demo...

Relationship between menstruation status and work conditions in Japan.

Science.gov (United States)

Nishikitani, Mariko; Nakao, Mutsuhiro; Tsurugano, Shinobu; Inoure, Mariko; Yano, Eiji

2017-01-01

Menstrual problems can significantly impact daily and work life. In reaction to a shrinking population, the Japanese government is encouraging more women to participate in the labor force. Actual success in achieving this aim, however, is limited. Specifically, participation in the workforce by women during their reproductive years is impacted by their health, which involves not only work conditions, but also traditional family circumstances. Therefore, it is important to further assess and gather more information about the health status of women who work during their reproductive years in Japan. Specifically, women's health can be represented by menstruation status, which is a pivotal indicator. In this study, we assessed the association between short rest periods in work intervals and menstruation and other health status indicators among female workers in Japan. Study participants were recruited from the alumnae of a university, which provided a uniform educational level. All 9864 female alumnae were asked to join the survey and 1630 (17%) accepted. The final sample of study participants ( n  = 505) were aged 23-43 years, had maintained the same job status for at least 1 year, and were not shift workers, had no maternal status, and did not lack any related information. The participants were divided into two groups according to interval time, with 11 h between end of work and resumption of daily work as a benchmark. This interval time was based on EU regulations and the goal set by the government of Japan. Health outcomes included: menstrual cycle, dysmenorrhoea symptoms, anxiety regarding health, and satisfaction in terms of health. Multiple logistic regression analyses were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for health indexes in association with interval time by adjusting for confounding variables that included both psychosocial and biological factors. We compared the health status of women in the workforce with

Screen for agents that induce autolysis in Bacillus subtilis.

Science.gov (United States)

Lacriola, Christopher J; Falk, Shaun P; Weisblum, Bernard

2013-01-01

The growing prevalence of antibiotic-resistant infections underscores the need to discover new antibiotics and to use them with maximum effectiveness. In response to these needs, we describe a screening protocol for the discovery of autolysis-inducing agents that uses two Bacillus subtilis reporter strains, SH-536 and BAU-102. To screen chemical libraries, autolysis-inducing agents were first identified with a BAU-102-based screen and then subdivided with SH-536 into two major groups: those that induce autolysis by their direct action on the cell membrane and those that induce autolysis secondary to inhibition of cell wall synthesis. SH-536 distinguishes between the two groups of autolysis-inducing agents by synthesizing and then releasing β-galactosidase (β-Gal) in late stationary phase at a time that cells have nearly stopped growing and are therefore tolerant of cell wall synthesis inhibitors. Four hits, named compound 2, compound 3, compound 5, and compound 24, obtained previously as inducers of autolysis by screening a 10,080-compound discovery library with BAU-102, were probed with SH-536 and found to release β-Gal, indicating that their mode of action was to permeabilize the B. subtilis cell membrane. The four primary hits inhibited growth in Staphylococcus aureus, Enterococcus faecium, Bacillus subtilis, and Bacillus anthracis, with MICs in the 12.5- to 25-μg/ml (20 to 60 μM) range. The four primary hits were further used to probe B. subtilis, and their action was partially characterized with respect to the dependence of induced autolysis on specific autolysins.

Menstruation in an unusual place: A case of thoracic endometriosis ...

African Journals Online (AJOL)

While pelvic endometriosis is relatively common, thoracic menstruation is rare. A report of what is believed to be the first case of thoracic endometriosis in Uganda is given. A 34 year old female was complaining of on and off chest pain mainly on the right side. Clinically she had signs of pleural effusion and 500 mls of altered ...

Do lunar phases influence menstruation? A year-long retrospective study.

Science.gov (United States)

Ilias, I; Spanoudi, F; Koukkou, E; Adamopoulos, D A; Nikopoulou, S C

2013-07-01

We assessed with cross-approximate entropy menstruation onset versus moon phases in 74 women with 980 menstrual cycles over a calendar year. In defiance of traditional beliefs and contrary to what some researchers have argued with short-term research work, in this long-term study we did not find any synchrony of lunar phases with the menstrual cycle.

How Menstruation Is Shaping Girls' Education in Rural Nepal

Science.gov (United States)

Basyal, Samrat

2016-01-01

With voices for women's education coming from around the globe, it is a real setback when girls are unable to attend schools during their menstruation or periods, a process they encounter every month. The absence of Nepalese rural female students from schools during their periods does not only have the biological aspect to it but incorporates a…

Associations of Age, BMI, and Years of Menstruation with Proximal Femur Strength in Chinese Postmenopausal Women: A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Huili Kang

2016-01-01

Full Text Available This study aimed to elucidate the associations of age, BMI, and years of menstruation with proximal femur strength in Chinese postmenopausal women, which may improve the prediction of hip fracture risk. A cross-sectional study was conducted in 1322 Chinese postmenopausal women recruited from communities. DXA images were used to generate bone mineral density (BMD and geometric parameters, including cross-sectional area (CSA, outer diameter (OD, cortical thickness (CT, section modulus (SM, buckling ratio (BR at the narrow neck (NN, intertrochanter (IT, and femoral shaft (FS. Relationships of age, BMI, and years of menstruation with bone phenotypes were analyzed with the adjustment of height, age at menarche, total daily physical activity, education, smoking status, calcium tablet intake, etc. Age was associated with lower BMD, CSA, CT, SM, and higher BR (p < 0.05, which indicated a weaker bone strength at the proximal femur. BMI and years of menstruation had the positive relationships with proximal femur strength (p < 0.05. Further analyses showed that the ranges of absolute value of change slope per year, per BMI or per year of menstruation were 0.14%–1.34%, 0.20%–2.70%, and 0.16%–0.98%, respectively. These results supported that bone strength deteriorated with aging and enhanced with higher BMI and longer time of years of menstruation in Chinese postmenopausal women.

The forecasting of menstruation based on a state-space modeling of basal body temperature time series.

Science.gov (United States)

Fukaya, Keiichi; Kawamori, Ai; Osada, Yutaka; Kitazawa, Masumi; Ishiguro, Makio

2017-09-20

Women's basal body temperature (BBT) shows a periodic pattern that associates with menstrual cycle. Although this fact suggests a possibility that daily BBT time series can be useful for estimating the underlying phase state as well as for predicting the length of current menstrual cycle, little attention has been paid to model BBT time series. In this study, we propose a state-space model that involves the menstrual phase as a latent state variable to explain the daily fluctuation of BBT and the menstruation cycle length. Conditional distributions of the phase are obtained by using sequential Bayesian filtering techniques. A predictive distribution of the next menstruation day can be derived based on this conditional distribution and the model, leading to a novel statistical framework that provides a sequentially updated prediction for upcoming menstruation day. We applied this framework to a real data set of women's BBT and menstruation days and compared prediction accuracy of the proposed method with that of previous methods, showing that the proposed method generally provides a better prediction. Because BBT can be obtained with relatively small cost and effort, the proposed method can be useful for women's health management. Potential extensions of this framework as the basis of modeling and predicting events that are associated with the menstrual cycles are discussed. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Uterine contraction induced by Ghanaian plants used to induce abortion

DEFF Research Database (Denmark)

Larsen, Birgitte HV; Soelberg, Jens; Kristiansen, Uffe

2016-01-01

Ethnomedicinal observations from the time of the Atlantic slave trade show women in Ghana historically used plants as emmenagogues (menstruation stimulants) and to induce abortion. This study investigates the effect of four of these plants on uterine contraction. The historically used plants were...

Menstruation and menstrual hygiene amongst adolescent school girls in Kano, Northwestern Nigeria.

Science.gov (United States)

Lawan, U M; Yusuf, Nafisa Wali; Musa, Aisha Bala

2010-09-01

This study examined the knowledge and practices of adolescent school girls in Kano, Nigeria around menstruation and menstrual hygiene. Data was collected quantitatively and analyzed using Epi info version 3.2.05. The mean age of the students was 14.4 +/- 1.2 years; majority was in their mid adolescence. The students attained menarche at 12.9 +/- 0.8 years. Majority had fair knowledge of menstruation, although deficient in specific knowledge areas. Most of them used sanitary pads as absorbent during their last menses; changed menstrual dressings about 1-5 times per day; and three-quarter increased the frequency of bathing. Institutionalizing sexuality education in Nigerian schools; developing and disseminating sensitive adolescent reproductive health massages targeted at both parents and their adolescent children; and improving access of the adolescents to youth friendly services are veritable means of meeting the adolescent reproductive health needs in Nigeria.

Pattern of teen menstruation among secondary school girls in south east Nigeria.

Science.gov (United States)

Nwokocha, Ada R C; Chinawa, Josephat M; Ubesie, Agozie C; Onukwuli, Vivian I; Manyike, Pius C

2016-03-01

Menstruation in the teenage age has assumed variable trends which is been influenced by several variables. This study is aimed at determining the pattern and trend of menstruation among teens attending secondary school in south east Nigeria and associated factors. Menstruation patterns were investigated using a stratified random sampling method of teens from junior secondary schools in Enugu, south east Nigeria. A self-administered questionnaire was developed and data analyzed using SPSS version 19. A total of 897 female teenagers aged 9-18 years completed the questionnaire with a mean age of 13.9±1.9 years. The mean age (SD) at onset of menarche was 12.5±1.2 years. Teenage girls with higher BMI achieved menarche earlier at age 8 and 9 when compared with their counterparts with lower BMI and this is statistically significant. F=7.60, df=8, p<0.001. Teens with a 14-day cycle had a higher BMI when compared with teens with longer cycle but this is not statistically significant. F=1.05, df=4, p=0.381. There is a statistical significance difference between teens duration of menstrual flow and BMI. Those with higher BMI had longer duration(4-5 days) compared with those with lower BMI. F=3.329, df=4, p=0.01 CONCLUSIONS: This study revealed that the mean age at onset of menarche was 12.5±1.2 years showing a continuing decreasing trend. Teens with higher BMI attain menarche earlier and had longer days of periods when compared with their counterpart with lower BMI.

A cross-sectional study to assess awareness about menstruation in adolescent girls of an urban slum in western Maharashtra.

Science.gov (United States)

Dudeja, Puja; Sindhu, Apoorva; Shankar, Pooja; Gadekar, Tukaram

2016-10-14

Reproductive health of adolescent girls is crucial as it determines the health of future generations. School girls when experiencing menarche find themselves in a setting without water, toilets or a supportive female teacher to explain the changes happening in their body. An important concern for adolescent girls is to have adequate, correct knowledge along with facilities and the cultural environment to manage menstruation hygienically and with dignity. Hence, the present study was done to assess knowledge and practices about menstruation in adolescent school girls of an urban slum. This was a descriptive cross-sectional study conducted among girls of a Government School located in an urban slum of western Maharashtra. A total of 250 girls participated. Data collection was through a pilot-tested questionnaire. The data thus collected were entered into Microsoft Excel and analyzed using the SPSS 20 software. All girls were educated about menstrual hygiene after the study. The mean age of the students was 14.9±1.75 years. The mean age at menarche was 11.97 (95% CI: 11.94-11.99). It was observed that only half (56.4%) had acquired prior knowledge about attaining menarche. Out of these in a large proportion, the knowledge was imparted to them by their mothers (60.7%), followed by friends (31.8%). There was no significant association between educational status of mother and awareness in respondent about menstruation. Regarding the organ of menstrual blood flow, half (50.7%) knew the correct answer (i.e. uterus); whereas the rest believed that it was stomach/kidney, etc. Most of the school girls (90.5%) used sanitary pads. Almost 90% of the young women faced physical complaints or health problems during menstruation. Most of the participants had some kind of restrictions on them during the menstruation and most of these were religious restrictions (69.7%) followed by physical (41.2%) and social restrictions (22.3%). All of them were unsatisfied with the toilets and

Menarche and menstruation through the eyes of pubescent students in eastern Taiwan: implications in sociocultural influence and gender differences issues.

Science.gov (United States)

Chang, Yu-Ting; Lin, Mei-Ling

2013-03-01

Menstruation is a significant part of women's lives. It has been studied from many perspectives to draw various conclusions about biological and physiological development, gender differences, and sociocultural environments. The purpose of this study was to explore how male and female pubescent students perceive and interpret menarche and menstruation and how their perceptions reflect gender differences and the sociocultural environment in eastern Taiwan. This was an exploratory qualitative study that employed focus group interviews. Data were collected from 20 girls and 27 boys, aged 10-12 years, who were recruited from two elementary schools. Participants engaged in 19 focus group discussions, which lasted 45-60 minutes each. Discussion transcripts were collected, encoded, categorized, and analyzed using the Atlas V 5.0 software. The central theme in menarche and menstruation experiences among pubescent students in eastern Taiwan can be summarized as, "Struggling to grow up amidst contradictions," an attitude that reflects gender divisions and sociocultural representations and practices. Generally, participants' views on menstruation fell within five subthemes: "Ambiguous," "Disregarded," "Dirty," "Personal," and "Transitional." These themes were analyzed within the contexts of society, school, and family. In line with previous research, this study shows the need for more individual reproductive health consultations, reliable sex education, and well-planned health policies to assist pubescent students manage menstruation. In addition, this study suggests that the subjugation of girls and women remains a critical issue that must be addressed and challenged.

Knowledge and self-care practices in adolescent girls living in Nablus district during menstruation: a cross-sectional study.

Science.gov (United States)

Shalabi-Abbas, Eatimad; Dweikat, Saba; Al Gazawy, Israa; Draghmah, Sajeda

2018-02-21

Menstruation is a natural phenomenon that occurs throughout the reproductive life of every woman. The aim of this study was to explore knowledge and self-care practices among Palestinian adolescent girls during their menstrual period. Reproductive health issues in adolescent girls is an important but neglected area of Palestinian research. For this cross-sectional study we recruited girls from grades seven, eight, and nine in the three biggest schools for girls in Nablus district. Participants were given a self-administered questionnaire that included questions about diet habits, daily activity, medication usage, and social norms related to the menstrual period. Data were analysed using SPSS version 17. The study protocol was approved ethically by Ibn Sina College for Health Sciences board. Verbal informed consent was obtained from the participants. 100 girls completed the questionnaire. 68 (68%) respondents referred to their mothers as the main source of information about dealing with menstrual periods. 52 (52%) respondents believed that salty food affects adversely on their health during the menstrual period, and 85 (85%) answered that showering is important during menstruation and that no harm comes from touching things during menstruation. 38 (38%) girls did not change food quality or quantity during menstruation, and 36 (36%) girls often take hot herbal drinks to relieve menstrual pain, whereas 63 (63%) girls reported use of analgesics. 94 (94%) respondents had a proper way of disposing of dirty pads. 45 (45%) girls said they used school toilets, 70 (70%) mentioned the availability of private doors, and 60 (60%) reported the availability of soap and water. Self-care practices during menstruation could be improved in adolescent Palestinian girls by establishing comprehensive puberty education programmes in schools and providing appropriate sanitation conditions in school toilets. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alkylating agent (MNU)-induced mutation in space environment

Science.gov (United States)

Ohnishi, T.; Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.

2001-01-01

In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons (Papio anubis).

Science.gov (United States)

Uchihashi, M; Bergin, I L; Bassis, C M; Hashway, S A; Chai, D; Bell, J D

2015-05-01

The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal microbiome compared to that of humans, which is most commonly dominated by Lactobacillus spp. We evaluated the influence of age, reproductive cycling status (cycling vs. non-cycling) and menstruation on the vaginal microbiome of 38 wild-caught, captive female olive baboons (Papio anubis) by culture-independent sequencing of the V3-V5 region of the bacterial 16S rRNA gene. All baboons had highly diverse vaginal microbial communities. Adult baboons had significantly lower microbial diversity in comparison to subadult baboons, which was attributable to decreased relative abundance of minor taxa. No significant differences were detected based on cycling state or menstruation. Predictive metagenomic analysis showed uniformity in relative abundance of metabolic pathways regardless of age, cycle stage, or menstruation, indicating conservation of microbial community functions. This study suggests that selection of an optimal vaginal microbial community occurs at puberty. Since decreased diversity occurs in both baboons and humans at puberty, this may reflect a general strategy for selection of adult vaginal microbial communities. Comparative evaluation of vaginal microbial community development and composition may elucidate mechanisms of community formation and function that are conserved across host species or across microbial community types. These findings have implications for host health, evolutionary biology, and microbe-host ecosystems. © 2015 Wiley Periodicals, Inc.

Influence of menstruation on the microbiota of healthy women's labia minora as analyzed using a 16S rRNA gene-based clone library method.

Science.gov (United States)

Shiraishi, Tsukasa; Fukuda, Kazumasa; Morotomi, Nobuo; Imamura, Yuri; Mishima, Junko; Imai, Shigeo; Miyazawa, Kiyoshi; Taniguchi, Hatsumi

2011-01-01

The aim of this study was to determine the influence of menstruation on the bacterial population of healthy Japanese women's vulvas, especially the labia minora. Labia minora swabs were obtained from 10 premenopausal, nonpregnant Japanese women at premenstruation and on day 2 of menstruation. Vaginal swabs were also obtained from 3 out of the 10 women. No significant difference was found in the average bacterial cell count between the menstruation and premenstruation samples. Molecular analysis using a 16S rRNA gene-based clone library method detected 22 genera from the labia minora swabs (total 20), with the genus Lactobacillus being predominant at both premenstruation and during menstruation in 7 out of the 10 women. Of the other 3 women, 2 showed various kinds of bacterial species, including oral and fecal bacteria, with Atopobium vaginae and Gardnerella vaginalis predominating in the remaining woman's vulva in both conditions. In total, 6 out of 10 cases (60%) showed significantly different microbiota of the labia minora between the two conditions. These results imply that menstruation may promote a distortion of the bacterial flora around the vulva, although it causes no significant increase of the bacterial count.

Hormonal contraception and regulation of menstruation: a study of young women's attitudes towards 'having a period'.

Science.gov (United States)

Newton, Victoria Louise; Hoggart, Lesley

2015-07-01

Irregular bleeding is one of the most common side effects of hormonal contraception and a key reason for the discontinuation of hormonal methods. A qualitative study in which 12 young women volunteered to be interviewed in depth, along with six focus group discussions (23 participants). The study had two main research objectives: to document and investigate what young women think and feel about menstruation and contraception, and to explore young women's preferences regarding the intersection of contraceptives and bleeding patterns. Although participants held a broad view that menstruation can be an inconvenience, they did ascribe positive values to having a regular bleed. Bleeding was seen as a signifier of non-pregnancy and also an innate part of being a woman. A preference for a 'natural' menstruating body was a strong theme, and the idea of selecting a hormonal contraceptive that might stop the bleeding was not overly popular, unless the young woman suffered with painful natural menstruation. Contraceptives that mimicked the menstrual cycle were acceptable to most, suggesting that cyclic bleeding still holds a symbolic function for women. When counselling young women about the effect of different contraceptive modalities on their bleeding, practitioners should explore how the women feel about their bleeding, including how they might feel if their bleeding stopped or if they experienced erratic bleeding patterns. Practitioners also need to recognise the subjective understanding of the 'natural body' as held by some women, and in these cases to support them in their seeking out of non-hormonal methods of contraception. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Menstruation and menstrual hygiene among adolescent girls of West Bengal, India: A school based comparative study

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Adrija Datta

2012-11-01

Full Text Available Background: Adolescents are often less informed, less experienced, and less comfortable accessing reproductive health information and services than adults. In many developing countries, a culture of silence surrounds the topic of menstruation and related issues; as a result many young girls lack appropriate and sufficient information regarding menstrual hygiene. This may result in incorrect and unhealthy behaviour during their menstrual period. Objectives: To assess and compare knowledge, belief, ideas, source of knowledge and practice of menstrual hygiene between school-going adolescents in an urban and a rural school of West Bengal, India. Methods: Cross-sectional, descriptive study was conducted among adolescent female students of Howrah district of West Bengal, India in the year 2011. Data was collected by pre-designed, pre-tested semi-structured self administered questionnaire. Results: The mean age at menarche was 12.1 years among urban and 12.2 years among the rural participants. More than 80% participants had some restrictions imposed during menstruation. Significantly higher number of urban girls had pre-menarchal knowledge on menstruation and used sanitary napkins. Conclusions: Menstrual hygiene is a vital aspect of health education for adolescent girls. For improvement of menstrual hygiene, sanitary napkins should be made universally available and affordable.

Menstruation and menstrual hygiene among adolescent girls of West Bengal, India: A school based comparative study

Directory of Open Access Journals (Sweden)

Adrija Datta

2012-01-01

Full Text Available Background: Adolescents are often less informed, less experienced, and less comfortable accessing reproductive health information and services than adults. In many developing countries, a culture of silence surrounds the topic of menstruation and related issues; as a result many young girls lack appropriate and sufficient information regarding menstrual hygiene. This may result in incorrect and unhealthy behaviour during their menstrual period. Objectives: To assess and compare knowledge, belief, ideas, source of knowledge and practice of menstrual hygiene between school-going adolescents in an urban and a rural school of West Bengal, India. Methods: Cross-sectional, descriptive study was conducted among adolescent female students of Howrah district of West Bengal, India in the year 2011. Data was collected by pre-designed, pre-tested semi-structured self administered questionnaire. Results: The mean age at menarche was 12.1 years among urban and 12.2 years among the rural participants. More than 80% participants had some restrictions imposed during menstruation. Significantly higher number of urban girls had pre-menarchal knowledge on menstruation and used sanitary napkins. Conclusions: Menstrual hygiene is a vital aspect of health education for adolescent girls. For improvement of menstrual hygiene, sanitary napkins should be made universally available and affordable.

Meanings and Experiences of Menstruation: Perceptions of Institutionalized Women with an Intellectual Disability

Science.gov (United States)

Chou, Yueh-Ching; Lu, Zxy-Yann Jane; Wang, Frank T. Y.; Lan, Chang-Fu; Lin, Li-Chan

2008-01-01

Background: No studies have ever been conducted concerning menstrual experiences among women with an intellectual disability in Taiwan. Materials and Methods: An in-depth interview was conducted at three public institutions and perceptions and experiences regarding menstruation were elicited from 55 women aged 21-65 years. Results: The…

Menstruation during and after caloric restriction: the 1944-1945 Dutch famine.

Science.gov (United States)

Elias, Sjoerd G; van Noord, Paulus A H; Peeters, Petra H M; den Tonkelaar, Isolde; Kaaks, Rudolf; Grobbee, Diederick E

2007-10-01

To investigate the relation between exposure to the 1944-45 Dutch famine and concurrent and subsequent menstrual disturbances. Cohort study. Doorlopend Onderzoek Mammacarcinoom breast cancer screening project, Utrecht, the Netherlands. Between 1983 and 1986, approximately 12,500 women (born 1911-41) reported their individual famine experiences. Irregular menstruation during the famine; time to regular menses after menarche, and menstrual patterns in adulthood after childhood famine. The famine had a direct impact on menstruation. The odds ratio (OR) of concurrent irregular menses in severely versus unexposed women was 8.85 (95% confidence interval [CI], 7.31-10.70). Women exposed to severe famine before menarche were 1.51 (95% CI, 1.15-1.98) times more likely to experience irregular menses for a prolonged time after menarche compared with the unexposed. This association was stronger in women with an early menarche. When the menstrual pattern was assessed in adulthood by menstrual diaries, a nonsignificant tendency of increased irregularity (OR, 1.13; 95% CI, 0.82-1.54) and regular but long menstrual cycles (OR, 1.41; 95% CI, 0.89-2.23) was observed in women exposed to severe famine. Famine relates to concurrent menstrual irregularity, and exposure in childhood seems to affect the subsequent menstrual pattern.

Radical-induced oxidation of RAFT agents : a kinetic study

NARCIS (Netherlands)

Li, Changxi; He, Junpo; Zhou, Yanwu; Gu, Yuankai; Yang, Yuliang

2011-01-01

Radical-induced oxidn. of reversible addn.-fragmentation chain transfer (RAFT) agents is studied with respect to the effect of mol. structure on oxidn. rate. The radicals are generated by homolysis of either azobisisobutyronitrile or alkoxyamine and transformed in situ immediately into peroxy

Lipoxygenase independent hexanal formation in isolated soy proteins induced by reducing agents.

Science.gov (United States)

Lei, Q; Boatright, W L

2008-08-01

Compared to corresponding controls, 6.5 mM dithiothreitol (DTT) elevated headspace hexanal level over aqueous slurries of both commercial isolated soy proteins (ISP) and laboratory ISP prepared with 80 degrees C treatment. Further analysis revealed that lipoxygenase (LOX) activity was not detected from these ISP, indicating that LOX is not involved in the observed hexanal increase. Levels of the induced headspace hexanal over the ISP aqueous slurries were proportional to the amount of DTT added in the range of 0 to 65 mM. Subsequent systematic investigations with model systems revealed that iron was required for the reducing agent-induced hexanal formation from linoleic acid. Erythorbate, another reducing agent, can also induce hexanal formation in both ISP and model systems. As a comparison, the LOX activity and hexanal synthesis in defatted soy flour were examined. The corresponding results showed that defatted soy flour maintained high LOX activities and that hexanal synthesis in such sample was significantly inhibited by high concentration DTT (above 130 mM). Data from the current investigation demonstrate the existence of LOX independent hexanal formation induced by reducing agents in ISP and the potential requirement of iron as a catalyst.

Feasibility and effectiveness of unintended pregnancy prevention with low-dose mifepristone combined with misoprostol before expected menstruation.

Science.gov (United States)

Li, Cui-Lan; Chen, Dun-Jin; Deng, Yi-Fan; Song, Li-Ping; Mo, Xue-Tang; Liu, Kai-Jie

2015-12-01

What is the efficacy of maintaining or restoring non-pregnant status with low-dose mifepristone combined with misoprostol administered before expected menstruation? Low-dose mifepristone and misoprostol administered at the time of expected menstruation was effective and safe in maintaining or restoring non-pregnant status, with no obvious menstrual disturbance. Menstrual regulation involves the medical or mechanical stimulation of uterine sloughing in women with up to 2-3 weeks of menstrual delay. Low-dose mifepristone plus misoprostol is efficacious for termination of ultra-early pregnancy (≤ 35 days of amenorrhoea) with no obvious menstrual disturbance. A total of 678 women fulfilled all criteria and were recruited. Seventeen women dropped out after deciding to remain pregnant and 11 others were lost to follow-up. Thus, data from 650 women who completed the procedure were included in analyses. Participants were enrolled at any time during their menstrual cycle and administered medication 1 day before expected menstruation. The end of the study was defined on a per-patient basis as the date of completion of the post-treatment menstrual cycle. The primary outcome was the efficacy of abortion induction (for pregnant women) or menstrual regulation (for non-pregnant women). Women with regular menstrual cycles (25-35 days) were voluntarily recruited for this study between February 2012 and December 2014. Serum β-hCG was measured before mifepristone intake. Mifepristone (50 mg) was administered orally 1 day before expected menstruation and 200 µg misoprostol was administered orally on the day of expected menstruation. Efficacy, disturbance in bleeding patterns in the treatment and post-treatment cycles, satisfaction with the treatment, and subsequent contraception preference were analysed. Retrospective analysis of serum β-hCG levels at admission indicated that 23.3% (158/678) of the women were pregnant. The success rate for pregnancy termination was 98.6% (136

Water, Sanitation and Hygiene Conditions in Kenyan Rural Schools: Are Schools Meeting the Needs of Menstruating Girls?

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Kelly T. Alexander

2014-05-01

Full Text Available Water, sanitation and hygiene (WASH programs in African schools have received increased attention, particularly around the potential impact of poor menstrual hygiene management (MHM on equity for girls’ education. This study was conducted prior to a menstrual feasibility study in rural Kenya, to examine current WASH in primary schools and the resources available for menstruating schoolgirls. Cross-sectional surveys were performed in 62 primary schools during unannounced visits. Of these, 60% had handwashing water, 13% had washing water in latrines for menstruating girls, and 2% had soap. Latrines were structurally sound and 16% were clean. Most schools (84% had separate latrines for girls, but the majority (77% had no lock. Non-governmental organizations (NGOs supported WASH in 76% of schools. Schools receiving WASH interventions were more likely to have: cleaner latrines (Risk Ratio (RR 1.5; 95% Confidence Intervals [CI] 1.0, 2.1, handwashing facilities (RR 1.6, CI 1.1, 2.5, handwashing water (RR 2.7; CI 1.4, 5.2, and water in girls’ latrines (RR 4.0; CI 1.4, 11.6. Schools continue to lack essential WASH facilities for menstruating girls. While external support for school WASH interventions improved MHM quality, the impact of these contributions remains insufficient. Further support is required to meet international recommendations for healthy, gender-equitable schools.

Abnormal structure and functional connectivity of the anterior insula at pain-free periovulation is associated with perceived pain during menstruation.

Science.gov (United States)

Dun, Wang-Huan; Yang, Jing; Yang, Ling; Ding, Dun; Ma, Xue-Ying; Liang, Feng-Li; von Deneen, Karen M; Ma, Shao-Hui; Xu, Xiao-Ling; Liu, Jixin; Zhang, Ming

2017-12-01

Neuroimaging studies have demonstrated the critical role of the insula in pain pathways and its close relation with the perceived intensity of nociceptive stimuli. We aimed to identify the structural and functional characteristics of the insula during periovulatory phase in women with primary dysmenorrhea (PDM), and further investigate its association with the intensity of perceived pain during menstruation. Optimized voxel-based morphometry and functional connectivity (FC) analyses were applied by using 3-dimensional T1-weighted and resting functional magnetic resonance imaging (fMRI) in 36 patients at the peri-ovulation phase and 29 age-, education-, and gender-matched healthy controls (HC). A visual analogue scale (VAS) was used to examine the intensity of the abdominal pain at periovulation and menstruation. In our results, PDM patients had significant higher VAS-rating during menstruaion than periovulation. Compared with the HC, PDM patients had lower gray matter density in the left anterior insula (aINS). Taken the left aINS as a seed region, we further found hypoconnectivity between aINS and medial prefrontal cortex (mPFC), which showed negative relation with the VAS during menstruation. As the aINS is a key site of the salience network (SN) and the mPFC is a critical region in the default mode network (DMN), it's implicated a trait-related central-alteration that communications between pain attention and perception networks were disrupted without the ongoing menstrual pain. Moreover, result of correlation analysis, at least in part, suggested a possible role of altered FC (pain-free period) in predicting pain perception (menstruation).

Impact of health education on knowledge and practices about menstruation among adolescent school girls of rural part of district Ambala, Haryana

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A Arora

2013-12-01

Full Text Available Background: This study was undertaken to assess the impact of health education on knowledge regarding menstruation, misconceptions related to it as the prevalence of RTI is still very high in India.  Aims: To study the existing level of status of hygiene, knowledge and practices regarding menstruation among adolescent school girls and to assess the change in their knowledge level and practices after health education. Materials A community-based pre and post interventional study was conducted among 200 adolescents’ girls of class IX and X of rural part of district Ambala. Multistage random sampling technique was used to draw the representative sample. A pre-tested questionnaire was administered and later health education regarding menstruation and healthy menstrual practices was imparted to the girls. Post-test was done after 3 months to assess the impact of health education. Pre- and post-intervention, data were compared using the paired t test, z test for proportions, chi-squared test for paired proportions. Difference between Proportions of the pre-post data and its 95% confidence interval has been calculated of the findings. SPSS for Windows software version 20 (IBM, Chicago, USA have been used for data analysis. The level of significance has been considered at p value 0.05 while in the post-test preceding health education, significant improvements were observed in their practices. Conclusion: Overall significant improvement was found in knowledge and practices regarding menstruation among adolescent school girls.

A Case of Rhabdomyolysis Induced by Lipid Lowering Agent

Energy Technology Data Exchange (ETDEWEB)

Koh, Eun Mi; Lee, Tae Won; Ihn, Chun Gyoo; Kim, Kwang Won; Kim, Myung Jae; Choi, Young Kil [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

1990-03-15

Bezafibrate is a lipid-lowering agent and one of the fabric acid derivatives. It is relatively safe and well tolerated and adverse reactions to bezafibrate have largely been restricted to gastrointestinal disturbances. But a few cases of rhabdomyolysis after bezafibrate administration have been reported and recently we experienced bezafibrate-induced rhabdomyolysis in patients with chronic renal failure. So we report this case with the bone scan finding and the literature review. We believe that this is the first case report of bezafibrate-induced rhabdomyolysis in Korea.

A Case of Rhabdomyolysis Induced by Lipid Lowering Agent

International Nuclear Information System (INIS)

Koh, Eun Mi; Lee, Tae Won; Ihn, Chun Gyoo; Kim, Kwang Won; Kim, Myung Jae; Choi, Young Kil

1990-01-01

Bezafibrate is a lipid-lowering agent and one of the fabric acid derivatives. It is relatively safe and well tolerated and adverse reactions to bezafibrate have largely been restricted to gastrointestinal disturbances. But a few cases of rhabdomyolysis after bezafibrate administration have been reported and recently we experienced bezafibrate-induced rhabdomyolysis in patients with chronic renal failure. So we report this case with the bone scan finding and the literature review. We believe that this is the first case report of bezafibrate-induced rhabdomyolysis in Korea.

Medically induced amenorrhea in female astronauts.

Science.gov (United States)

Jain, Varsha; Wotring, Virginia E

2016-01-01

Medically induced amenorrhea can be achieved through alterations in the normal regulatory hormones via the adoption of a therapeutic agent, which prevents menstrual flow. Spaceflight-related advantages for medically induced amenorrhea differ according to the time point in the astronaut's training schedule. Pregnancy is contraindicated for many pre-flight training activities as well as spaceflight, therefore effective contraception is essential. In addition, the practicalities of menstruating during pre-flight training or spaceflight can be challenging. During long-duration missions, female astronauts have often continuously taken the combined oral contraceptive pill to induce amenorrhea. Long-acting reversible contraceptives (LARCs) are safe and reliable methods used to medically induce amenorrhea terrestrially but as of yet, not extensively used by female astronauts. If LARCs were used, daily compliance with an oral pill is not required and no upmass or trash would need disposal. Military studies have shown that high proportions of female personnel desire amenorrhea during deployment; better education has been recommended at recruitment to improve uptake and autonomous decision-making. Astronauts are exposed to similar austere conditions as military personnel and parallels can be drawn with these results. Offering female astronauts up-to-date, evidence-based, comprehensive education, in view of the environment in which they work, would empower them to make informed decisions regarding menstrual suppression while respecting their autonomy.

A critical period of progesterone withdrawal precedes menstruation in macaques

Science.gov (United States)

Slayden, Ov D; Brenner, Robert M

2006-01-01

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents.

Science.gov (United States)

Grob, J J; Collet, A M; Bonerandi, J J

1989-01-01

A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders.

Nature of chromosome gaps induced by alkylating agents and γ-rays as revealed by caffeine treatment

International Nuclear Information System (INIS)

Dimitrov, B.

1981-01-01

In the cells of primary roots of Crepis capillaris, post-treatment with caffeine increased the frequency of gaps and chromosomal aberrations induced by the alkylating agents ethyleneimine and N-nitroso-N-methylurethane and γ-rays. The increase in the frequency of gaps was considerably lower than that observed in chromosomal aberrations, this being more strongly expressed in the case fo the alkylating agents. The potentiating effect of caffeine on the γ-ray-induced chromosomal gaps was a little higher in S as compared in G 2 . These results lead to the conclusion that the alkylating agents and the γ-rays might induce 2 types of chromosomal gap. (orig.)

The Nature and Extent of Help Given to Women with Intellectual Disabilities to Manage Menstruation

Science.gov (United States)

Rodgers, Jackie; Lipscombe, Jo

2005-01-01

Menstruation has been shown to be problematic for many women with intellectual disabilities. There has been a greater focus on menstrual suppression or elimination than on help and training to manage menstrual care successfully. A cross-sectional questionnaire survey was conducted in England to investigate the help and training currently given to…

Premenarcheal Mexican Girls' and Their Teachers' Perceptions of Preparation Students Receive about Menstruation at School.

Science.gov (United States)

Marvan, Luisa; Bejarano, Janett

2005-01-01

This survey explored how fifth-grade Mexican premenarcheal girls (N = 80) and their teachers (N = 16) view the preparation students receive about menstruation at school. The most discussed topics in class included hygiene and body functions. The main discrepancies between girls and teachers were as follows: (a) more teachers than girls reported…

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

OpenAIRE

Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in th...

Basal concentrations of oestradiol may predict the outcome of in-vitro maturation in regularly menstruating women

DEFF Research Database (Denmark)

Mikkelsen, A L; Andersson, A M; Skakkebaek, N E

2001-01-01

Retrospectively it was examined whether the number of retrieved oocytes, the maturation rate and cleavage rate can be predicted in regularly menstruating women by the use of the following predictive variables on cycle day 3-4: the concentration of FSH, oestradiol, inhibin B and inhibin A in serum...

Complement-induced histamine release from human basophils. III. Effect of pharmacologic agents.

Science.gov (United States)

Hook, W A; Siraganian, R P

1977-02-01

Human serum activated with zymosan generates a factor (C5a) that releases histamine from autologous basophils. Previously we have presented evidence that this mechanism for C5a-induced release differs from IgE-mediated reactions. The effect of several pharmacologic agents known to alter IgE-mediated release was studied to determine whether they have a similar action on serum-induced release. Deuterium oxide (D2O), which enhances allergic release, inhibited in a concentration-dependent fashion the serum-induced reaction at incubation temperatures of 25 and 32 degrees C. The colchicine-induced inhibition was not reversed by D2O. Cytochalasin B, which gives a variable enhancement of IgE-mediated release, had a marked enhancing effect on the serum-induced reaction in all subjects tested. The following agents known to inhibit the IgE-mediated reaction also inhibited serum-induced release at 25 degrees C: colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine, and 2-deoxy-D-glucose. These results suggest that the serum-induced release is modulated by intracellular cyclic AMP, requires energy, and is enhanced by the disruption of microfilaments. The lack of an effect by D2O would suggest that microtubular stabilization is not required. The data can be interpreted to indicate that IgE- and C5a-mediated reactions diverge at a late stage in the histamine release pathway.

A study on the menstruation of Korean adolescent girls in Seoul

Directory of Open Access Journals (Sweden)

Jin Chul Lee

2011-05-01

Full Text Available Purpose : Westernized eating habits have been associated with earlyage menstruation, which increases the incidence of dysmenorrhea and premenstrual syndrome among adolescent girls. We therefore surveyed changes in menarche timing and the general menstrual characteristics of adolescent girls in Seoul, Korea. Methods : We surveyed 538 teenage girls who visited our hospital between July and November 2007. Items explored included age at menarche, general menstrual characteristics, occurrence of premenstrual syndrome and treatment thereof, and an association between present dysmenorrhea and a family history of the condition. Results : Average age at menarche was 12.6 years, with 29% (n=156 subjects beginning menstruation at age 12 years. The prevalence of dysmenorrhea was 82% (n=435. The main symptoms were abdominal (53.2% and lower back pain (34.2%, and 15.2% of girls who experienced such symptoms required medication. Present dysmenorrhea, and a family history thereof, were statistically correlated (P&lt;0.05. In addition, 58.8% (n=316 of teenage girls had symptoms of premenstrual syndrome. The most frequent psychological symptoms were fatigue (36.4% and nervousness (38.7%, whereas the most common physical symptom was menstrual cramps (46.5%. Most subjects (87.6% tolerated the symptoms of premenstrual syndrome without medication; 11.4% took medicines including painkillers; but only 0.1% of subjects visited a doctor. Conclusion : The average age at menarche in Korean girls was 12.6 years, thus younger than in the past. Most teenage girls experienced dysmenorrhea and premenstrual syndrome, but few consulted a doctor. Organized treatment plans are required to manage menstrual problems in teenage girls.

Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrol.

Science.gov (United States)

Parker, Samantha E; Troisi, Rebecca; Wise, Lauren A; Palmer, Julie R; Titus-Ernstoff, Linda; Strohsnitter, William C; Hatch, Elizabeth E

2014-02-01

Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause. The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations. Participants were 5573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models. Osteoporosis was the main outcome measure. The IRRs for osteoporosis incidence with age at menarche less than 11 years and age at menopause of 50 years or younger were 0.82 (CI 0.59, 1.14) and 0.61 (CI 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR 1.80; CI 1.14, 2.86) compared with 35 years or more of menstruation. Associations were stronger among women who had not been prenatally exposed to DES. Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.

Vaginal Repair of Cesarean Section Scar Diverticula that Resulted in Improved Postoperative Menstruation.

Science.gov (United States)

Zhou, Jieru; Yao, Min; Wang, Husheng; Tan, Weilin; Chen, Pin; Wang, Xipeng

2016-01-01

Owing to the increase in cesarean sections (C-sections) worldwide, long-term complications such as postmenstrual spotting, chronic pelvic pain, and C-section scar ectopic pregnancies have created a new medical era of gynecologic disease. A new type of vaginal repair is evaluated to repair C-section diverticulum (CSD) and rebuild the muscular layer to improve symptoms of abnormal uterine bleeding and decrease the risk of uterine rupture. Retrospective cohort study (Canadian Task Force classification II-2). University hospital. A total of 121 patients with CSD diagnoses by transvaginal ultrasound (TVU) presented with postmenstrual spotting between June 2012 and March 2015. All patients had undergone at least 1 C-section delivery and had no history of postmenstrual spotting before undergoing C-section. Vaginal excision and suture of CSD. The mean duration of menstruation was 14.87 ± 3.46 days preoperatively and decreased to 8.22 ± 2.73 days at 1 month after surgery, 8.89 ± 2.67 days at 3 months after surgery, and 9.02 ± 2.47 days at 6 months after surgery (p menstruation and imaging data did not differ markedly between 3 months and 6 months, suggesting that follow-up at 3 months represents an adequate endpoint for evaluating the effectiveness of surgery. At 6 months, 80.3% of patients (94 of 117) reached ≤10 days of menstruation. Further study revealed that a TRM at 6 months of ≥8.5 mm measured by TVU (relative risk [RR], 6.418; 95% confidence interval [CI], 1.478-28.443) and an interval between CS and vaginal repair of ≤2.5 years (RR, 12.0; 95% CI, 1.541- 93.454) were good prognostic factors associated with surgery. Vaginal repair of CSD improved the symptoms of postmenstrual spotting and anatomically corrected the scars. An interval between C-section and a surgery of ≤2.5 years was optimal for vaginal repair, and a TRM at 6 months of ≥8.5 mm represented the standard healing of CSD. Copyright © 2016 AAGL. Published by

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Delay-Induced Consensus and Quasi-Consensus in Multi-Agent Dynamical Systems

NARCIS (Netherlands)

Yu, Wenwu; Chen, Guanrong; Cao, Ming; Ren, Wei

2013-01-01

This paper studies consensus and quasi-consensus in multi-agent dynamical systems. A linear consensus protocol in the second-order dynamics is designed where both the current and delayed position information is utilized. Time delay, in a common perspective, can induce periodic oscillations or even

Sorbitol as an efficient reducing agent for laser-induced copper deposition

Science.gov (United States)

Kochemirovsky, V. A.; Logunov, L. S.; Safonov, S. V.; Tumkin, I. I.; Tver'yanovich, Yu. S.; Menchikov, L. G.

2012-10-01

We have pioneered in revealing the fact that sorbitol may be used as an efficient reducing agent in the process of laser-induced copper deposition from solutions; in this case, it is possible to obtain copper lines much higher quality than by using conventional formalin.

Managing menstruation in the workplace: an overlooked issue in low- and middle-income countries.

OpenAIRE

Sommer, Marni; Chandraratna, Sahani; Cavill, Sue; Mahon, Therese; Phillips-Howard, Penelope

2016-01-01

The potential menstrual hygiene management barriers faced by adolescent girls and women in workplace environments in low- and middle-income countries has been under addressed in research, programming and policy. Despite global efforts to reduce poverty among women in such contexts, there has been insufficient attention to the water and sanitation related barriers, specifically in relation to managing monthly menstruation, that may hinder girls? and women?s contributions to the workplace, and ...

Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar Surfaces of Living Plants Maintained in a Surety Hood

Science.gov (United States)

2016-09-01

RAIN-INDUCED WASH-OFF OF CHEMICAL WARFARE AGENT (VX) FROM FOLIAR SURFACES OF LIVING PLANTS MAINTAINED IN A...Final 3. DATES COVERED (From - To) May 2014 – Sep 2015 4. TITLE AND SUBTITLE Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar...galli Foliage Chemical warfare agent (CWA) O-ethyl-S-(2

Study on the identification method of chemical warfare agents with spectroscopy of neutron induced γ rays

International Nuclear Information System (INIS)

Liu Boxue; Li Yun; Li Xiangbao

1996-01-01

The paper briefly describes some non-destructive verification technologies of chemical warfare agents in-site, and some application of neutron induced gamma ray analysis, such as multi-elements analysis of coal, hidden explosive detection and identification of chemical agents. It also describes some problems in developing the portable isotopic neutron spectroscopy for non-destructive evaluation of chemical warfare agents

The impact of menstruation in adolescents with disabilities related to cerebral palsy.

Science.gov (United States)

Zacharin, Margaret; Savasi, Ingrid; Grover, Sonia

2010-07-01

Information regarding menstrual difficulties for adolescents with developmental disabilities and their families is limited. To assess the impact of menstruation on adolescents with developmental disabilities and their families, and to compare this to previously reported experiences of age-matched normal girls. Families of girls aged 12-18 years with known disabilities, attending the Royal Children's Hospital, Melbourne, were recruited into a questionnaire based study evaluating issues of menstruation and associated problems, together with the consequent psychological, social and emotional impact on their families and carers. Information was sought regarding menstrual management strategies, outcome satisfaction and specific areas of family concern. 103 questionnaires were completed. The average age of participating girls was 15.11 years, mean menarchal age 12.3 years. 79 girls were postmenarchal. The severity of menstrual problems was similar to a normal population. 59 (76%) were happy with the impact of menses on their social activities. More than 50% sought menstrual advice before menarche. Advice seeking strongly correlated with disability severity (p=0.01) and impact of menses on social activities (p=0.01), which in turn were highly predictive of seeking assistance (p=0.005). Carer satisfaction with current management inversely correlated with treatment seeking behaviour (p=0.034). Menstrual characteristics in this population are similar to those without disabilities. There is a high level of parental anxiety regarding the impact of menses, particularly when disability is severe. Medical therapies may be required but information for families is lacking. Clinicians should play a proactive and educational role with families and adolescents with disabilities.

Detection of biological warfare agents using ultra violet-laser induced fluorescence LIDAR.

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Joshi, Deepti; Kumar, Deepak; Maini, Anil K; Sharma, Ramesh C

2013-08-01

This review has been written to highlight the threat of biological warfare agents, their types and detection. Bacterial biological agent Bacillus anthracis (bacteria causing the disease anthrax) which is most likely to be employed in biological warfare is being discussed in detail. Standoff detection of biological warfare agents in aerosol form using Ultra violet-Laser Induced Fluorescence (UV-LIF) spectroscopy method has been studied. Range-resolved detection and identification of biological aerosols by both nano-second and non-linear femto-second LIDAR is also discussed. Calculated received fluorescence signal for a cloud of typical biological agent Bacillus globigii (Simulants of B. anthracis) at a location of ~5.0 km at different concentrations in presence of solar background radiation has been described. Overview of current research efforts in internationally available working UV-LIF LIDAR systems are also mentioned briefly. Copyright © 2013 Elsevier B.V. All rights reserved.

Knowledge, Practices, and Restrictions Related to Menstruation among Young Women from Low Socioeconomic Community in Mumbai, India

Science.gov (United States)

Thakur, Harshad; Aronsson, Annette; Bansode, Seema; Stalsby Lundborg, Cecilia; Dalvie, Suchitra; Faxelid, Elisabeth

2014-01-01

The main objective was to assess knowledge, practices, and restrictions faced by young women regarding their menstrual hygiene. The views of adult women having young daughters were also included and both views were compared. In addition, the factors influencing the menstrual hygiene practices were also studied. The study was carried out during 2008 in Mumbai, India. The mixed methods approach was followed for the data collection. Both qualitative and quantitative methods were used to collect the data. For quantitative survey, totally 192 respondents (96 adult and 96 younger women) were selected. While young women were asked about questions related to their menstruation, adult women were asked questions to find out how much they know about menstrual history of their daughters. The qualitative data helped to supplement the findings from the quantitative survey and to study the factors affecting menstrual practices in young women. The mean age at menarche reported was 13.4 years and 30–40% of young girls did not receive any information about menstruation before menarche. It is thus seen that very few young girls between the age group 15 and 24 years did receive any information before the onset of menstruation. Among those who received some information, it was not adequate enough. The source of information was also not authentic. Both young and adult women agreed on this. Due to the inadequate knowledge, there were certain unhygienic practices followed by the young girls resulting in poor menstrual hygiene. It also leads to many unnecessary restrictions on young girls and they faced many health problems and complaints, which were either ignored or managed inappropriately. The role of health sector was almost negligible from giving information to the management of health problems of these young girls. This paper reemphasizes the important, urgent, and neglected need of providing correct knowledge to the community including adolescent girls. PMID:25072044

Knowledge, Practices, and Restrictions Related to Menstruation among Young Women from Low Socioeconomic Community in Mumbai, India.

Science.gov (United States)

Thakur, Harshad; Aronsson, Annette; Bansode, Seema; Stalsby Lundborg, Cecilia; Dalvie, Suchitra; Faxelid, Elisabeth

2014-01-01

The main objective was to assess knowledge, practices, and restrictions faced by young women regarding their menstrual hygiene. The views of adult women having young daughters were also included and both views were compared. In addition, the factors influencing the menstrual hygiene practices were also studied. The study was carried out during 2008 in Mumbai, India. The mixed methods approach was followed for the data collection. Both qualitative and quantitative methods were used to collect the data. For quantitative survey, totally 192 respondents (96 adult and 96 younger women) were selected. While young women were asked about questions related to their menstruation, adult women were asked questions to find out how much they know about menstrual history of their daughters. The qualitative data helped to supplement the findings from the quantitative survey and to study the factors affecting menstrual practices in young women. The mean age at menarche reported was 13.4 years and 30-40% of young girls did not receive any information about menstruation before menarche. It is thus seen that very few young girls between the age group 15 and 24 years did receive any information before the onset of menstruation. Among those who received some information, it was not adequate enough. The source of information was also not authentic. Both young and adult women agreed on this. Due to the inadequate knowledge, there were certain unhygienic practices followed by the young girls resulting in poor menstrual hygiene. It also leads to many unnecessary restrictions on young girls and they faced many health problems and complaints, which were either ignored or managed inappropriately. The role of health sector was almost negligible from giving information to the management of health problems of these young girls. This paper reemphasizes the important, urgent, and neglected need of providing correct knowledge to the community including adolescent girls.

Algal bloom sedimentation induces variable control of lake eutrophication by phosphorus inactivating agents

Energy Technology Data Exchange (ETDEWEB)

Wang, Changhui [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Bai, Leilei [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Graduate University of Chinese Academy of Sciences (China); Jiang, He-Long, E-mail: hljiang@niglas.ac.cn [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China); Xu, Huacheng [State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008 (China)

2016-07-01

Lake eutrophication typically occurs with a syndrome of algae breeding and biomass accumulation (e.g., algal blooms). Therefore, the effect of algal bloom sedimentation on eutrophication control by phosphorus (P) inactivating agents was assessed herein. Three commercial products, including aluminum (Al) sulfate, iron (Fe) sulfate, and a lanthanum-modified clay (Phoslock®), as well as one easily available by-product, drinking water treatment residue (DWTR), were selected. The most important finding was that during algae sedimentation, P immobilization from the overlying water by Al, Phoslock®, and DWTR was dominated by a long-term slow phase (> 150 d), while Fe has limited effectiveness on the immobilization. Further analysis indicated that the algae sedimentation effect was mainly due to the slow release of P from algae, leading to relatively limited P available for the inactivating agents. Then, a more unfavorable effect on the P immobilization capability of inactivating agents was caused by the induced anaerobic conditions, the released organic matter from algae, and the increased sulfide in the overlying water and sediments during sedimentation. Overall, algae sedimentation induced variable control of eutrophication by P inactivating agents. Accordingly, recommendations for future works about algal lake restoration were also proposed. - Highlights: • A long-term P immobilization by Phoslock®, DWTR, and Al was observed. • Fe had limited effectiveness on P pollution control for overlying water. • Al and Fe enhanced sulfur reduction, while DWTR and Phoslock® had minor effect. • The sedimentation reduced Al and La release from agents, but enhanced Fe release. • The agents changed organic matter compositions and structures in water columns.

Algal bloom sedimentation induces variable control of lake eutrophication by phosphorus inactivating agents

International Nuclear Information System (INIS)

Wang, Changhui; Bai, Leilei; Jiang, He-Long; Xu, Huacheng

2016-01-01

Lake eutrophication typically occurs with a syndrome of algae breeding and biomass accumulation (e.g., algal blooms). Therefore, the effect of algal bloom sedimentation on eutrophication control by phosphorus (P) inactivating agents was assessed herein. Three commercial products, including aluminum (Al) sulfate, iron (Fe) sulfate, and a lanthanum-modified clay (Phoslock®), as well as one easily available by-product, drinking water treatment residue (DWTR), were selected. The most important finding was that during algae sedimentation, P immobilization from the overlying water by Al, Phoslock®, and DWTR was dominated by a long-term slow phase (> 150 d), while Fe has limited effectiveness on the immobilization. Further analysis indicated that the algae sedimentation effect was mainly due to the slow release of P from algae, leading to relatively limited P available for the inactivating agents. Then, a more unfavorable effect on the P immobilization capability of inactivating agents was caused by the induced anaerobic conditions, the released organic matter from algae, and the increased sulfide in the overlying water and sediments during sedimentation. Overall, algae sedimentation induced variable control of eutrophication by P inactivating agents. Accordingly, recommendations for future works about algal lake restoration were also proposed. - Highlights: • A long-term P immobilization by Phoslock®, DWTR, and Al was observed. • Fe had limited effectiveness on P pollution control for overlying water. • Al and Fe enhanced sulfur reduction, while DWTR and Phoslock® had minor effect. • The sedimentation reduced Al and La release from agents, but enhanced Fe release. • The agents changed organic matter compositions and structures in water columns.

The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

Science.gov (United States)

Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

2015-01-01

Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

Agent-based simulation for human-induced hazard analysis.

Science.gov (United States)

Bulleit, William M; Drewek, Matthew W

2011-02-01

Terrorism could be treated as a hazard for design purposes. For instance, the terrorist hazard could be analyzed in a manner similar to the way that seismic hazard is handled. No matter how terrorism is dealt with in the design of systems, the need for predictions of the frequency and magnitude of the hazard will be required. And, if the human-induced hazard is to be designed for in a manner analogous to natural hazards, then the predictions should be probabilistic in nature. The model described in this article is a prototype model that used agent-based modeling (ABM) to analyze terrorist attacks. The basic approach in this article of using ABM to model human-induced hazards has been preliminarily validated in the sense that the attack magnitudes seem to be power-law distributed and attacks occur mostly in regions where high levels of wealth pass through, such as transit routes and markets. The model developed in this study indicates that ABM is a viable approach to modeling socioeconomic-based infrastructure systems for engineering design to deal with human-induced hazards. © 2010 Society for Risk Analysis.

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection.

Science.gov (United States)

Kyrou, Dimitra; Kolibianakis, Efstratios M; Fatemi, Human M; Camus, Michel; Tournaye, Herman; Tarlatzis, Basil C; Devroey, Paul

2011-10-01

To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). Prospective study. University. One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Reframing menstruation in India: metamorphosis of the menstrual taboo with the changing media coverage.

Science.gov (United States)

Yagnik, Arpan Shailesh

2014-01-01

In this study I hypothesize metamorphosis of the menstrual taboo by examining the image and perception shifts of two social taboos-HIV/AIDS and homosexuality-from estranged taboos to embraced social issues. Trends identified in their media framing and respective image shifts were applied to menstruation in India. Based on my understanding of theory, topic, and geographical location, I construct a metamorphosis. I contribute the hypothesized final stage of metamorphosis, and explain how framing is likely instrumental in bringing about these changes.

Military women's attitudes toward menstruation and menstrual suppression in relation to the deployed environment: development and testing of the MWATMS-9 (short form).

Science.gov (United States)

Trego, Lori L; Jordan, Patricia J

2010-01-01

To determine military women's attitudes toward menstruation and menstrual suppression with oral contraceptives in the deployed environment. A cross-sectional descriptive design with the administration of the Menstrual Attitude Questionnaire (MAQ) and the 55-item Military Women's Attitudes Towards Menstrual Suppression Scale (MWATMS) to a convenience sample (n = 278) of women in the U.S. Army with deployment experience. The MAQ's five subscales' mean scores ranged from 3.4 (+/-1.11) to 5.1 (+/-1.06), indicating neutral to moderate attitudes toward menstruation. Measurement development on the MWATMS produced a nine-item scale with three components: stress effects, benefits to self, and environmental barriers. Menstrual attitudes were generally neutral in this sample; however, military women favor menstrual suppression during deployment owing to the effects of stress during deployment, benefits that suppression would provide, and the barriers to menstrual hygiene in the deployed environment. Women who perceived menstruation as bothersome and debilitating had positive attitudes toward menstrual suppression. These findings can contribute to appropriate predeployment women's health care and improve the readiness for deployment in female soldiers. Providers should educate women on the risks and benefits of menstrual suppression methods and provide guidance on impact that the deployed environment can have on their menstrual experiences.

Predictors of female worker attitudes towards menstruation and the provision of help to institutionalized women with intellectual disabilities in Taiwan.

Science.gov (United States)

Chou, Yueh-Ching; Lu, Zxy-yann J; Pu, Cheng-yun; Lan, Chung-Fu

2008-08-01

No previous research has examined the importance of both individual and environmental factors for predicting caregivers' menstrual attitudes. To explore the predictors of female caregivers' attitudes towards menstruation and the help they give to women with intellectual disabilities, we conducted a cross-sectional questionnaire survey which was completed by 725 female workers from 12 institutions in Taiwan. The Menstrual Attitudes Questionnaire (MAQ) and a structured questionnaire were used. Logistic regression analysis revealed that individual characteristics such as age and education were significantly associated with menstrual attitudes of female caregivers working with institutionalized women with intellectual disabilities. Furthermore, the environmental context, such as the frequency of discussions with colleagues, training in menstrual management care and the level of difficulty when giving help in menstruation management, was important for improving caregivers' menstrual attitudes. This study contributes to the existing literature by determining both individual and environmental predictors of caregivers' menstrual attitudes.

Understanding and defining sanitation insecurity: women’s gendered experiences of urination, defecation and menstruation in rural Odisha, India

Science.gov (United States)

Clasen, Thomas F; Hadley, Craig; Yount, Kathryn M; Haardörfer, Regine; Rout, Manaswini; Dasmohapatra, Munmun; Cooper, Hannah LF

2017-01-01

Background Research suggests that the lived experience of inadequate sanitation may contribute to poor health outcomes above and beyond pathogen exposure, particularly among women. The goal of this research was to understand women’s lived experiences of sanitation by documenting their urination-related, defecation-related and menstruation-related concerns, to use findings to develop a definition of sanitation insecurity among women in low-income settings and to develop a conceptual model to explain the factors that contribute to their experiences, including potential behavioural and health consequences. Methods We conducted 69 Free-List Interviews and eight focus group discussions in a rural population in Odisha, India to identify women’s sanitation concerns and to build an understanding of sanitation insecurity. Findings We found that women at different life stages in rural Odisha, India have a multitude of unaddressed urination, defecation and menstruation concerns. Concerns fell into four domains: the sociocultural context, the physical environment, the social environment and personal constraints. These varied by season, time of day, life stage and toilet ownership, and were linked with an array of adaptations (ie, suppression, withholding food and water) and consequences (ie, scolding, shame, fear). Our derived definition and conceptual model of sanitation insecurity reflect these four domains. Discussion To sincerely address women’s sanitation needs, our findings indicate that more is needed than facilities that change the physical environment alone. Efforts to enable urinating, defecating and managing menstruation independently, comfortably, safely, hygienically, privately, healthily, with dignity and as needed require transformative approaches that also address the gendered, sociocultural and social environments that impact women despite facility access. This research lays the groundwork for future sanitation studies to validate or refine the proposed

'Gushing Out Blood': Defloration and Menstruation in Memoirs of a Woman of Pleasure.

Science.gov (United States)

Read, Sara

2018-06-01

John Cleland's 1740s pornographic novel, Memoirs of a Woman of Pleasure repeatedly depicts and eroticises the act of defloration. As such it is a revealing illustration of what Ivan Bloch termed the 'defloration mania' of the eighteenth century. This article maps narrative events on to contemporary medical depictions of first intercourse to show the ways that the theories and ideas presented in medical and pseudo-medical texts transferred into erotic fiction and demonstrates how in some instances the bloody defloration scenes can be read as being sex during menstruation, an act which was culturally forbidden at this time.

Hypertension induced by chemotherapeutic and immunosuppresive agents: a new challenge.

Science.gov (United States)

Abi Aad, Simon; Pierce, Matthew; Barmaimon, Guido; Farhat, Fadi S; Benjo, Alexandre; Mouhayar, Elie

2015-01-01

Hypertension is a common adverse effect of certain anti neoplastic therapy. The incidence and severity of hypertension are dependent mainly on the type and the dose of the drug. We reviewed the literature for studies that reported the effect of anti neoplastic agents on blood pressure in patients with malignancies. The medical databases of PubMed, MEDLINE and EMBASE were searched for articles published in English between 1955 and June 2012. The effects of specific agents on blood pressure were analyzed. Hypertension is a prevalent adverse effect of many of the new chemotherapy agents such as VEGF inhibitors. Approximately 30% of patients treated for cancer will have concomitant hypertension, and crucial chemotherapy can sometimes be stopped due to new onset or worsening severe hypertension. The importance of a timely diagnosis and optimal management of HTN in this group of patients is related to the facts that HTN is a well established risk factor for chemotherapy-induced cardiotoxicity and if left untreated, can alter cancer management and result in dose reductions or termination of anti-cancer treatments as well as life-threatening end organ damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents1

Science.gov (United States)

Biroccio, Annamaria; Benassi, Barbara; Fiorentino, Francesco; Zupi, Gabriella

2004-01-01

Abstract Here we investigate the mechanism(s) involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH) content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by l-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, and concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent drug-induced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Bax/cytochrome c redistribution. The relationship among c-Myc, GSH content, and the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis. PMID:15153331

Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention 

Directory of Open Access Journals (Sweden)

Łukasz Dobrek

2012-09-01

Full Text Available The use of oxazaphosphorines (cyclophosphamide, ifosfamide in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite – acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation.The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned. 

Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

National Research Council Canada - National Science Library

Shih, Tsung-Ming; Rowland, Tami C; McDonough, John H

2007-01-01

Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl...

Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

International Nuclear Information System (INIS)

Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

2006-01-01

Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, α-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, γ-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

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Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

2016-06-01

In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

International Nuclear Information System (INIS)

Nishi, Yoshisuke; Miyanaga, Kumiko; Sato, Sei-ichi; Inui, Naomichi

1990-01-01

The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with 60 Co γ-rays also induced DNA strand breaks. The elution profiles for γ-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than γ-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice. (Author)

DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

Energy Technology Data Exchange (ETDEWEB)

Nishi, Yoshisuke (Japan Tobacco Inc., Yokohama (Japan). Central Research Inst.); Miyanaga, Kumiko; Sato, Sei-ichi (Japan Tobacco Inc., Hatano, Kanagawa (Japan). Toxicology Research Lab.); Inui, Naomichi (Japan Tobacco Inc., Yokohama, Kanagawa (Japan). Pharmaceutical Research Labs.)

1990-01-01

The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with {sup 60}Co {gamma}-rays also induced DNA strand breaks. The elution profiles for {gamma}-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than {gamma}-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice. (Author).

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

Energy Technology Data Exchange (ETDEWEB)

Mouret, Stéphane, E-mail: stephane.mouret@irba.fr [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Dorandeu, Frédéric [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Ecole du Val-de-Grâce, 1 place Alphonse Laveran, Paris (France); Boudry, Isabelle [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France)

2013-10-15

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

Science.gov (United States)

Goswami, Dinesh G; Kant, Rama; Tewari-Singh, Neera; Agarwal, Rajesh

2018-09-01

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Transfection Agent Induced Nanoparticle Cell Loading

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Karin Montet-Abou

2005-07-01

Full Text Available Loading cells with magnetic nanoparticles, and tracking their fate in vivo by high resolution MRI, is an attractive approach for enhancing the efficacy of cell-based therapies including those utilizing hematopoietic stem cells, neuroprogenitor cells, and T cells. The transfection agent (internalization agent assisted loading with the Feridex IV® nanoparticle is an attractive method of loading because of the low cost of materials, and possible low regulatory barriers for eventual clinical use. We therefore explored the interaction between Feridex IV® and three internalization agents protamine (PRO, polylysine (PLL, and lipofectamine (LFA. Feridex reacted with internalization agents to form aggregates, except when either the internalization agent or Feridex was present in large excess. When Jurkat T cells were incubated with Feridex/LFA or Feridex/PRO mixtures, and washed by centrifugation, nanoparticle aggregates co-purified with cells. With C17.2 cells large iron oxide particles adhered to the cell surface. At 30 μg/mL Feridex and 3 μg/mL LFA, internalization was largely mediated by LFA and was largely cytoplasmic. However, we found that the conditions used to label cells with Feridex and transfection agents need to be carefully selected to avoid the problems of surface adsorption and nanoparticle precipitation.

Development of Autoimmune Overt Hypothyroidism Is Highly Associated With Live Births and Induced Abortions but Only in Premenopausal Women

DEFF Research Database (Denmark)

Carle, Allan; Pedersen, Inge Buelow; Knudsen, Nils

2014-01-01

: In conditional multivariate logistic regression models, we analyzed the associations between the development of autoimmune hypothyroidism and age at menarche/menopause, years of menstruations, pregnancies, spontaneous and induced abortions, live births, and years on oral contraceptives and postmenopausal hormone...

Dietary agents in the prevention of alcohol-induced hepatotoxicty: preclinical observations.

Science.gov (United States)

Shivashankara, Arnadi Ramachandrayya; Azmidah, Aysha; Haniadka, Raghavendra; Rai, Manoj Ponadka; Arora, Rajesh; Baliga, Manjeshwar Shrinath

2012-02-01

Long term alcohol consumption is one of the important causes for liver failure and death. To complicate the existing problem there are no dependable hepatoprotective drugs and a large number of patients prefer using complementary and alternative medicines for treating and managing hepatic complications. Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed "Let food be thy medicine and medicine be thy food." Exploring the association between diet and health continues even today. Preclinical studies carried out in the recent past have shown that the commonly used dietary agents like Allium sativum (garlic), Camellia sinensis (tea), Curcuma longa (turmeric), Emblica officinalis (Indian gooseberry), Ferula asafoetida (asafoetida), Garcinia cambogia (Malabar tamarind), Glycine max (soyabean), Murraya koenigii (curry leaves), Piper betle (beetle leaf), Prunus armeniaca (apricot), Ocimum gratissimum (wild basil), Theobroma cacao (cocoa), Trigonella foenum-graecum (fenugreek) and Vitis vinifera (grapes) protect against ethanol-induced hepatotoxicity. Mechanistic studies have shown that the beneficial effects of these phytochemicals in preventing the ethanol-induced hepatotoxicity are mediated by the antioxidant, free radical scavenging, anti-inflammatory and anti-fibrotic effects. The present review for the first time collates the hepatoprotective effects of these agents and also emphasizes on aspects that need future research to establish their utility in humans.

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes.

Science.gov (United States)

RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

2014-04-04

Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2×LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and

Mucin2 is Required for Probiotic Agents-Mediated Blocking Effects on Meningitic E. coli-Induced Pathogenicities.

Science.gov (United States)

Yu, Jing-Yi; He, Xiao-Long; Puthiyakunnon, Santhosh; Peng, Liang; Li, Yan; Wu, Li-Sha; Peng, Wen-Ling; Zhang, Ya; Gao, Jie; Zhang, Yao-Yuan; Boddu, Swapna; Long, Min; Cao, Hong; Huang, Sheng-He

2015-10-01

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl- L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5- Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

Cluster headache in women: relation with menstruation, use of oral contraceptives, pregnancy, and menopause

Science.gov (United States)

van Vliet, J A; Favier, I; Helmerhorst, F M; Haan, J; Ferrari, M D

2006-01-01

In contrast with migraine, little is known about the relation between cluster headache and menstrual cycle, oral contraceptives, pregnancy, and menopause. A population based questionnaire study was performed among 224 female cluster headache patients, and the possible effect of hormonal influences on cluster headache attacks studied. For control data, a similar but adjusted questionnaire was sent to healthy volunteers and migraine patients. It was found that menstruation, use of oral contraceptives, pregnancy, and menopause had a much smaller influence on cluster headache attacks than in migraine. Cluster headache can, however, have a large impact on individual women, for example to refrain from having children. PMID:16407458

Leukocyte changes across menstruation, ovulation, and mid-luteal phase and association with sex hormone variation.

Science.gov (United States)

Nowak, Judyta; Borkowska, Barbara; Pawlowski, Boguslaw

2016-09-10

Total leukocyte count (white blood cells-WBC) and the count of each subpopulation vary across the menstrual cycle, but results of studies examining the time and direction of these changes are inconsistent and methodologically flawed. Besides, no previous study focused on leukocyte count on the day of ovulation. Blood samples were obtained from 37 healthy and regularly cycling women aged 19.8-36.1 years. Samples were taken three times: during menstruation (M), ovulation (O), and in the mid-luteal phase (ML). WBC, neutrophils, lymphocytes, mixed cells, progesterone (P,) and estradiol (E) were measured in each of the three target phases of the cycle. Compared to menstruation, WBC (P = 0.002) and neutrophils (P < 0.001) increased around ovulation and remained stable in the mid-luteal phase, whereas lymphocyte and mixed cell counts did not change throughout the menstrual cycle. There were some correlations of sex hormone variation with leukocyte changes between M and O (positive for E and WBC, negative for P and WBC and for P and neutrophil count; P < 0.05), but not between O and ML. Peripheral leukocyte changes taking place in the second half of the cycle are already observable on the day of ovulation and they are associated with sex hormone variation. We speculate that these changes may lead to increased immune protection against pathogens at a time when fertilization and implantation typically occur. Am. J. Hum. Biol. 28:721-728, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evaluating of the Anticonvulsant Gabapentin against Nerve Agent-Induced Seizures in a Guinea Pig Model

Science.gov (United States)

2010-07-01

treating neuropathic pain. This study evaluated whether gabapentin could terminate or moderate nerve agent-induced seizures using a validated guinea ... pig model. Male Hartley guinea pigs were surgically prepared to record electroencephalographic (EEG) activity. After a week recovery, animals were

Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

Directory of Open Access Journals (Sweden)

Arroyo-Pardo Eduardo

2011-10-01

Full Text Available Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141 was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852 and two in the HFE gene (C282Y, H63D, explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

Magnetic resonance imaging of morphological and functional changes of the uterus induced by sacral surface electrical stimulation

International Nuclear Information System (INIS)

Ogura, Takahide; Murakami, Takashi; Ozawa, Yuka; Seki, Kazunori; Handa, Yasunobu

2006-01-01

The purpose of this study is to examine the morphological and kinematical changes of the uterus induced by electrical stimulation applied to the skin just above the second and fourth posterior sacral foramens (sacral surface electrical stimulation [ssES]) in 26 healthy subjects. Out of them, eight subjects who had severe pain subjectively during every menstruation received ssES just in menstruation. Morphological and functional changes of the uterus were examined by using T2-weighted magnetic resonance (MR) imaging and T1-weighted MR cinematography, respectively. Cyclic electrical stimulation for 15 min with 5 sec ON and 5 sec OFF was applied just before MR scanning. A decrease in thickness of the muscular layer of the uterus was observed in every subject after ssES for 15 min and was significant as compared with the thickness before ssES. Periodic uterine movement during menstruation was observed in the subjects with severe menstrual pain in MR cine and the power spectrum analysis of the movement showed a marked decrease in peak power and frequency after ssES treatment. We conclude that ssES causes a reduction of static muscle tension of the uterus in all menstrual cycle periods and suppression of uterine peristalsis during menstruation in the subjects with severe menstrual pain. Possible neural mechanisms for these static and dynamic effects of ssES on the uterus at spinal level are discussed. (author)

Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

Directory of Open Access Journals (Sweden)

Pallebage-Gamarallage Menuka

2012-09-01

Full Text Available Abstract Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA compromises blood–brain barrier (BBB integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG and amyloid-β enriched apolipoprotein (apo-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble. Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

Relationship of Level of Functioning of Institutionalized Women on a Task Analysis of Personal Care for Menstruation and the Adaptive Behavior Scale.

Science.gov (United States)

Brekke, Beverly W.; And Others

A 40-item behavior analysis task, the Menstrual Care Scale, was developed and tested with 75 randomly selected institutionalized severely retarded women (13-59 years old). The need for developing personal care skills in menstruation habits had been identified as a priority area for sexuality instruction by staff and confirmed by analysis of…

Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

Science.gov (United States)

Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

2014-01-01

Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: Prevention by thiol group protecting agents

International Nuclear Information System (INIS)

Custodio, Jose B.A.; Cardoso, Carla M.P.; Santos, Maria S.; Almeida, Leonor M.; Vicente, Joaquim A.F.; Fernandes, Maria A.S.

2009-01-01

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca 2+ -induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20 nmol/mg protein) induced Ca 2+ -dependent mitochondrial swelling, depolarization of membrane potential (ΔΨ), Ca 2+ release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40 nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the ΔΨ, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H 2 O 2 generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca 2+ -induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to

[Menstruation, inflammation and comorbidities: implications for woman health].

Science.gov (United States)

Graziottin, A; Zanello, P P

2015-02-01

Menstruation is the genital sign of systemic endocrine events. Heterogeneity of perimenstrual symptoms is associated with levels of inflammation, triggered by the fall of estrogens at genital and systemic level. Aim of the review is to concisely analyze the evidence on: 1) genital and systemic endocrine and inflammatory events associated with periods and perimenstrual symptoms; 2) rationale of intervention to reduce their intensity and impact on women's lives. This review of the literature, selected with a clinical perspective, supports the inflammatory basis of the menstrual event, triggered by the estrogens' and progesterone' fall. Moreover, the review analyzes the endocrine and inflammatory basis of perimenstrual pelvic and extrapelvic symptoms such as: menstrual pain, menstrual irregularities, premenstrual syndrome, gastrointestinal symptoms, catamenial headache, depression, perimenstrual myalgia, joint pain, allergies and asthma, heavy menstrual bleeding, associated ironless anemia, brain and behavioral consequences. Inflammation, with increase of cytokines and other markers, is modulated by the degranulation of mast cells at the basal level of the endometrium, in the blood, in all the organs where mast-cell are already activated from local pathologies and within the brain. The shift of inflammation from physiological to a pathologic intensity increases the severity of perimenstrual symptoms. Symptoms persist, moderately attenuated, also during the hormone free interval (HFI) in contraception. The HFI reduction from seven to two days significantly reduces menstrual inflammation and associated symptoms.

Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile

Directory of Open Access Journals (Sweden)

Konstantin V. Kudryavtsev

2014-01-01

Full Text Available This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents.

Science.gov (United States)

Kaina, Bernd; Christmann, Markus; Naumann, Steffen; Roos, Wynand P

2007-08-01

O(6)-methylguanine-DNA methyltransferase (MGMT) plays a crucial role in the defense against alkylating agents that generate, among other lesions, O(6)-alkylguanine in DNA (collectively termed O(6)-alkylating agents [O(6)AA]). The defense is highly important, since O(6)AA are common environmental carcinogens, are formed endogenously during normal cellular metabolism and possibly inflammation, and are being used in cancer therapy. O(6)AA induced DNA damage is subject to repair, which is executed by MGMT, AlkB homologous proteins (ABH) and base excision repair (BER). Although this review focuses on MGMT, the mechanism of repair by ABH and BER will also be discussed. Experimental systems, in which MGMT has been modulated, revealed that O(6)-methylguanine (O(6)MeG) and O(6)-chloroethylguanine are major mutagenic, carcinogenic, recombinogenic, clastogenic and killing lesions. O(6)MeG-induced clastogenicity and cell death require MutS alpha-dependent mismatch repair (MMR), whereas O(6)-chloroethylguanine-induced killing occurs independently of MMR. Extensive DNA replication is required for O(6)MeG to provoke cytotoxicity. In MGMT depleted cells, O(6)MeG induces apoptosis almost exclusively, barely any necrosis, which is presumably due to the remarkable ability of secondarily formed DNA double-strand breaks (DSBs) to trigger apoptosis via ATM/ATR, Chk1, Chk2, p53 and p73. Depending on the cellular background, O(6)MeG activates both the death receptor and the mitochondrial apoptotic pathway. The inter-individual expression of MGMT in human lymphocytes is highly variable. Given the key role of MGMT in cellular defense, determination of MGMT activity could be useful for assessing a patient's drug sensitivity. MGMT is expressed at highly variable amounts in human tumors. In gliomas, a correlation was found between MGMT activity, MGMT promoter methylation and response to O(6)AA. Although the human MGMT gene is inducible by glucocorticoids and genotoxins such as radiation and

Reexposure to the Amnestic Agent Alleviates Cycloheximide-Induced Retrograde Amnesia for Reactivated and Extinction Memories

Science.gov (United States)

Briggs, James F.; Olson, Brian P.

2013-01-01

We investigated whether reexposure to an amnestic agent would reverse amnesia for extinction of learned fear similar to that of a reactivated memory. When cycloheximide (CHX) was administered immediately after a brief cue-induced memory reactivation (15 sec) and an extended extinction session (12 min) rats showed retrograde amnesia for both…

Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

Science.gov (United States)

Albers, D S; Sonsalla, P K

1995-12-01

Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate

Steroids Regulate CXCL4 in the Human Endometrium During Menstruation to Enable Efficient Endometrial Repair.

Science.gov (United States)

Maybin, Jacqueline A; Thiruchelvam, Uma; Madhra, Mayank; Saunders, Philippa T K; Critchley, Hilary O D

2017-06-01

Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. To determine the presence/regulation of CXCL4 in the human endometrium as a putative repair factor at menses. Endometrial tissue was collected throughout the menstrual cycle from healthy women attending the gynecology department. Menstrual blood loss was objectively measured in a subset, and heavy menstrual bleeding (HMB) was defined as >80 mL per cycle. Monocytes were isolated from peripheral blood. CXCL4 messenger RNA (mRNA) and protein were identified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The function/regulation of endometrial CXCL4 was explored by in vitro cell culture. CXCL4 mRNA concentrations were significantly increased during menstruation. Intense staining for CXCL4 was detected in late secretory and menstrual tissue, localized to stromal, epithelial and endothelial cells. Colocalization identified positive staining in CD68+ macrophages. Treatment of human endometrial stromal and endothelial cells (hESCs and HEECs, respectively) with steroids revealed differential regulation of CXCL4. Progesterone withdrawal resulted in significant increases in CXCL4 mRNA and protein in hESCs, whereas cortisol significantly increased CXCL4 in HEECs. In women with HMB, CXCL4 was reduced in endothelial cells during the menstrual phase compared with women with normal menstrual bleeding. Cortisol-exposed macrophages displayed increased chemotaxis toward CXCL4 compared with macrophages incubated with estrogen or progesterone. These data implicate CXCL4 in endometrial repair after menses. Reduced cortisol at the time of menses may contribute to delayed endometrial repair and HMB, in part by mechanisms involving aberrant expression of CXCL4. Copyright © 2017 by the Endocrine Society

Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

International Nuclear Information System (INIS)

Onodera, Akira; Kawai, Yuichi; Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio

2013-01-01

Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

Energy Technology Data Exchange (ETDEWEB)

Onodera, Akira, E-mail: onodera@pharm.kobegakuin.ac.jp [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kawai, Yuichi [Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2013-06-14

Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

[Alkylating agents].

Science.gov (United States)

Pourquier, Philippe

2011-11-01

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Risk Stratification of iodine-induced thyrotoxicosis before contrast agent application

International Nuclear Information System (INIS)

Fricke, E.

2004-01-01

Today, examinations using iodine containing contrast media are rather frequent. Even though in modern contrast agents the content of free iodine is low, in vivo deiodination results in a non physiologic high iodine load of the thyroid gland. Whilst in normal thyroid tissue iodine metabolism and hormone production are self-regulating in spite of the variable iodine load, those mechanisms are disturbed in autonomous thyroid tissue. Clinical studies displayed low risk of iodine induced thyrotoxicosis after application of contrast agent. Nonetheless the clinician has to assess the risk of thyrotoxicosis for each individual patient and he has to decide how to cope with this risk. Thyroid scintigraphy using Tc-99m-pertechnetate with quantitative measurement of the thyroidal uptake (TcTU) has been shown to be a useful tool in this question, especially when performed under suppression of the non-autonomous tissue (TcTUs). In particular patients with pre-existing suppression of the TSH secretion should be selected for this investigation. Also at risk are elderly persons and those with diffuse or nodular goitres. In spite of the high frequency of contrast agent applications, data on scintigraphy for risk evaluation of thyrotoxicosis and on efficacy of prophylactic medication are scarce. Based on own results and on a review of literature, the risk of thyrotoxicosis seems to be negligible in patients with a TcTUs of less than 1% even in case of preexistent latent hyperthyroidism. If a suppressed TSH level is known and TcTUs is higher than 1%, prophylactic medication should be given. There is evidence for a combination therapy inhibiting both iodine uptake and metabolism, i.e. with perchlorate and thiamazole, being more efficient than monotherapy, particularly in patients with high risk of thyrotoxicosis. (orig.)

Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents.

Science.gov (United States)

Navari, Rudolph M

2003-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Although the 5-HT3 receptor antagonists, dexamethasone, and metoclopramide have been used to prevent delayed CINV, only dexamethasone appears to have much efficacy with acceptable toxicity. Recent studies have introduced two new agents, palonosetron and aprepitant, for the prevention of both acute and delayed CINV. Palonosetron is a new 5-HT3 receptor antagonist with a longer half life and a higher binding affinity than older 5-HT3 receptor antagonists. It improves the complete response rate (no emesis, no need for rescue) of acute and delayed CINV in patients receiving moderately emetogenic chemotherapy compared to the older 5-HT3 receptor antagonists. The other agent, aprepitant, is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when compared to placebo and when used in combination with dexamethasone compared to dexamethasone alone. Acute and delayed nausea may also be improved by aprepitant when used in combination with a 5-HT3 and dexamethasone prechemotherapy or with daily dosing for 3-5 days following chemotherapy. Based on these studies, new guidelines for the prevention of CINV are proposed. Future studies may consider the use of

Quantitative and subcellular localization analysis of the nuclear isoform dUTP pyrophosphatase in alkylating agent-induced cell responses

International Nuclear Information System (INIS)

Hu, Xiaolan; Yu, Yingnian; Li, Qian; Wu, Danxiao; Tan, Zhengning; Wang, Cheng; Wang, Jvping; Wu, Meiping

2011-01-01

Highlights: → MNNG-induced appearance of DUT-N in the extracellular fluid has cellular specificity. → MNNG alters the subcellular distribution of DUT-N in human cells in different ways. → DUT-N may be a potential biomarker to assess the risk of alkylating agents exposure. -- Abstract: Our previous proteome analysis showed that the nuclear isoform of dUTP pyrophosphatase (DUT-N) was identified in the culture medium of human amnion FL cells after exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These results suggest that DUT-N may be a potential early biomarker to assess the risk of alkylating agents exposure. DUT-N is one of the two isoforms of deoxyuridine triphosphate nucleotidohydrolase (dUTPase). Our current knowledge of DUT-N expression in human cells is very limited. In the current study, we first investigated the appearance of DUT-N in the culture medium of different human cell lines in response to a low concentration of MNNG exposure. We verified that the MNNG-induced appearance of DUT-N in the extracellular environment is cell-specific. Western blot analysis confirmed that the intracellular DUT-N changes responded to MNNG in a concentration-dependent and cell-specific manner. Furthermore, subcellular fraction experiments showed that 0.25 μM MNNG treatment dramatically increased the DUT-N expression levels in the cytoplasmic extracts prepared from both FL and HepG2 cells, increased DUT-N levels in nuclear extracts prepared from HepG2 cells, and decreased DUT-N levels in nuclear extracts from FL cells. Morphological studies using immunofluorescence showed that a low concentration of MNNG could alter the distribution of DUT-N in FL and HepG2 cells in different ways. Taken together, these studies indicate a role of DUT-N in alkylating agent-induced cell responses.

Detailed clinical and molecular study of 20 females with Xq deletions with special reference to menstruation and fertility.

Science.gov (United States)

Mercer, Catherine L; Lachlan, Katherine; Karcanias, Alexandra; Affara, Nabeel; Huang, Shuwen; Jacobs, Patricia A; Thomas, N Simon

2013-01-01

Integrity of the long arm of the X chromosome is important for maintaining female fertility and several critical regions for normal ovarian function have been proposed. In order to understand further the importance of specific areas of the X chromosome, we describe a series of 20 previously unreported patients missing part of Xq in whom detailed phenotypic information has been gathered as well as precise chromosome mapping using array Comparative Genomic Hybridization. Features often associated with Turner syndrome were not common in our study and excluding puberty, menarche and menstruation, the phenotypes observed were present in only a minority of women and were not specific to the X chromosome. The most frequently occurring phenotypic features in our patients were abnormalities of menstruation and fertility. Larger terminal deletions were associated with a higher incidence of primary ovarian failure, occurring at a younger age; however patients with similar or even identical deletions had discordant menstrual phenotypes, making accurate genetic counselling difficult. Nevertheless, large deletions are likely to be associated with complete skewing of X inactivation so that the resulting phenotypes are relatively benign given the amount of genetic material missing, even in cases with unbalanced X;autosome translocations. Some degree of ovarian dysfunction is highly likely, especially for terminal deletions extending proximal to Xq27. In conjunction with patient data from the literature, our study suggests that loss of Xq26-Xq28 has the most significant effect on ovarian function. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Nearest neighbor affects G:C to A:T transitions induced by alkylating agents.

OpenAIRE

Glickman, B W; Horsfall, M J; Gordon, A J; Burns, P A

1987-01-01

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference ...

'We keep it secret so no one should know'--a qualitative study to explore young schoolgirls attitudes and experiences with menstruation in rural western Kenya.

Science.gov (United States)

Mason, Linda; Nyothach, Elizabeth; Alexander, Kelly; Odhiambo, Frank O; Eleveld, Alie; Vulule, John; Rheingans, Richard; Laserson, Kayla F; Mohammed, Aisha; Phillips-Howard, Penelope A

2013-01-01

Keeping girls in school offers them protection against early marriage, teen pregnancy, and sexual harms, and enhances social and economic equity. Studies report menstruation exacerbates school-drop out and poor attendance, although evidence is sparse. This study qualitatively examines the menstrual experiences of young adolescent schoolgirls. The study was conducted in Siaya County in rural western Kenya. A sample of 120 girls aged 14-16 years took part in 11 focus group discussions, which were analysed thematically. The data gathered were supplemented by information from six FGDs with parents and community members. Emergent themes were: lack of preparation for menarche; maturation and sexual vulnerability; menstruation as an illness; secrecy, fear and shame of leaking; coping with inadequate alternatives; paying for pads with sex; and problems with menstrual hygiene. Girls were unprepared and demonstrated poor reproductive knowledge, but devised practical methods to cope with menstrual difficulties, often alone. Parental and school support of menstrual needs is limited, and information sparse or inaccurate. Girls' physical changes prompt boys and adults to target and brand girls as ripe for sexual activity including coercion and marriage. Girls admitted 'others' rather than themselves were absent from school during menstruation, due to physical symptoms or inadequate sanitary protection. They described difficulties engaging in class, due to fear of smelling and leakage, and subsequent teasing. Sanitary pads were valued but resource and time constraints result in prolonged use causing chafing. Improvised alternatives, including rags and grass, were prone to leak, caused soreness, and were perceived as harmful. Girls reported 'other girls' but not themselves participated in transactional sex to buy pads, and received pads from boyfriends. In the absence of parental and school support, girls cope, sometimes alone, with menarche in practical and sometimes hazardous

Disturbances of immunological homeostasis induced by radioactive iodine agents

International Nuclear Information System (INIS)

Anokhin, Yu.N.; Norets, T.A.

1986-01-01

(CBAxC57B1/6)F 1 mice were injected with 125 I and 131 I-sodium iodide at a dose of 5.74x10 4 Bq/g. For a long time after such treatment the animals manifested an increased level of spleen cells humoral immune response to a foreign antigen (sheep erythrocytes). The autoreactivity of spleen and lymph node lymphocytes to autologous erythrocytes was also elevated. At the same time the selective migration of 51 Cr-labeled spleen lymphocytes to the peripheral lymphoid organs was suppressed. The use of a model system of adoptive cell transfer revealed an increase in the functional activity of cells suppressing a humoral response in mice treated with radiopharmaceuticals. The most pronounced disturbances of immunological reactivity in mice took place 6 mos. after the beginning of the experiment. The results obtained indicated that mechanisms of immune response regulation played a certain role in disturbances of immunological homeostasis induced by radioactive iodine agents

Regulation of radiation protective agents on cell damage induced by reactive oxygen species

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Hee; Lee, Si Eun; Ju, Eun Mi; Gao, Eu Feng [Kyung Hee University, Seoul (Korea)

2002-04-01

In this study, we developed candidates of new radio-protective agents and elucidated the regulation mechanism of these candidates on cell damage induced by reactive oxygen species. The methanol extracts and ethylacetate fractions of NP-1, NP-5, NP-7, NP-11, NP-12 and NP-14 showed higher radical scavenging activity. The extracts of NP-7, NP-12 and NP-14 showed strong protective effect against oxidative damage induced by UV and H{sub 2}O{sub 2}. The most of samples enhanced SOD, CAT and GPX activity in V79-4 cells. The protective effect of samples on H{sub 2}O{sub 2}-induced apoptosis was observed with microscope and flow cytometer. Cells exposed to H{sub 2}O{sub 2} exhibit distinct morphological features of programmed cell death, such as nuclear fragmentation and increase in the percentage of cells with a sub-G1 DNA content. However, cells which was pretreated with samples significantly reduced the characteristics of apoptotic cells. Their morphological observation and DNA profiles were similar to those of the control cells. NP-14 which had excellent antioxidant activity restored G2/M arrest induced by oxidative stress. These data suggested that natural medicinal plants protected H{sub 2}O{sub 2}-induced apoptosis. 42 refs., 29 figs., 11 tabs. (Author)

Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.

Science.gov (United States)

Wu, Ren-Rong; Jin, Hua; Gao, Keming; Twamley, Elizabeth W; Ou, Jian-Jun; Shao, Ping; Wang, Juan; Guo, Xiao-Feng; Davis, John M; Chan, Philip K; Zhao, Jing-Ping

2012-08-01

Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia. Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis. A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group. Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.

Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

Science.gov (United States)

Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

2015-04-01

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

Directory of Open Access Journals (Sweden)

Ye Han

2015-01-01

Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Chemical hybridizing agent SQ-1-induced male sterility in Triticum aestivum L.: a comparative analysis of the anther proteome.

Science.gov (United States)

Liu, Hongzhan; Zhang, Gaisheng; Wang, Junsheng; Li, Jingjing; Song, Yulong; Qiao, Lin; Niu, Na; Wang, Junwei; Ma, Shoucai; Li, Lili

2018-01-05

Heterosis is widely used to increase the yield of many crops. However, as wheat is a self-pollinating crop, hybrid breeding is not so successful in this organism. Even though male sterility induced by chemical hybridizing agents is an important aspect of crossbreeding, the mechanisms by which these agents induce male sterility in wheat is not well understood. We performed proteomic analyses using the wheat Triticum aestivum L.to identify those proteins involved in physiological male sterility (PHYMS) induced by the chemical hybridizing agent CHA SQ-1. A total of 103 differentially expressed proteins were found by 2D-PAGE and subsequently identified by MALDI-TOF/TOF MS/MS. In general, these proteins had obvious functional tendencies implicated in carbohydrate metabolism, oxidative stress and resistance, protein metabolism, photosynthesis, and cytoskeleton and cell structure. In combination with phenotypic, tissue section, and bioinformatics analyses, the identified differentially expressed proteins revealed a complex network behind the regulation of PHYMS and pollen development. Accordingly, we constructed a protein network of male sterility in wheat, drawing relationships between the 103 differentially expressed proteins and their annotated biological pathways. To further validate our proposed protein network, we determined relevant physiological values and performed real-time PCR assays. Our proteomics based approach has enabled us to identify certain tendencies in PHYMS anthers. Anomalies in carbohydrate metabolism and oxidative stress, together with premature tapetum degradation, may be the cause behind carbohydrate starvation and male sterility in CHA SQ-1 treated plants. Here, we provide important insight into the mechanisms underlying CHA SQ-1-induced male sterility. Our findings have practical implications for the application of hybrid breeding in wheat.

Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

International Nuclear Information System (INIS)

Isobe, Ichiro; Maeno, Yoshitaka; Nagao, Masataka; Iwasa, Mineo; Koyama, Hiroyoshi; Seko-Nakamura, Yoshimi; Monma-Ohtaki, Jun

2003-01-01

There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders

Thermally induced self-healing epoxy/glass laminates with porous layers containing crystallized healing agent

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T. Szmechtyk

2018-07-01

Full Text Available Porous glass fiber and paper layers were tested for application in thermally induced self healing epoxy laminates as healing porous layers. Both types of layers were impregnated using high purity bisphenol A diglycidyl ether (BADGE epoxy with ability to crystallize during storage under 25 °C. Absorption capacity of porous layers was evaluated. Differential scanning calorimetry was used to investigate BADGE healing agent recrystallization process. Healing porous glass layers (HPGL were selected for further tests. Liquid chromatography and Fourier transform infrared (FT IR spectroscopy provided information about average molecular mass of embedded healing agent and functional groups in HPGL layers. Self-healing efficiency of three different laminates with HPGL layers was calculated based on the results of three-point bending test and Charpy impact test. Also, flexural properties and impact strength of laminates were evaluated. The obtained results confirm competitive self healing ability of composites with HPGL.

Influence of Diet, Menstruation and Genetic Factors on Iron Status: A Cross-Sectional Study in Spanish Women of Childbearing Age

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Ruth Blanco-Rojo

2014-03-01

Full Text Available The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142. Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC. Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene; rs1375515 (CACNA2D3 gene; and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively. Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26; women with mild iron deficiency (Cluster 2, n = 59 and women with normal iron status (Cluster 3, n = 57. Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001. In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age.

Science.gov (United States)

Blanco-Rojo, Ruth; Toxqui, Laura; López-Parra, Ana M; Baeza-Richer, Carlos; Pérez-Granados, Ana M; Arroyo-Pardo, Eduardo; Vaquero, M Pilar

2014-03-06

The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142). Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively). Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26); women with mild iron deficiency (Cluster 2, n = 59) and women with normal iron status (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

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Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

2009-08-06

Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing

Comparative Evaluation of the Effect of Menstruation, Pregnancy and Menopause on Salivary Flow Rate, pH and Gustatory Function.

Science.gov (United States)

Saluja, Pulin; Shetty, Vishwaprakash; Dave, Aparna; Arora, Manpreet; Hans, Vibha; Madan, Ajay

2014-10-01

There are five situations in a women's life during which hormone fluctuations make them more susceptible to oral health problems - during puberty, at certain points in the monthly menstrual cycle, when using birth control pills, during pregnancy, and at menopause. The present study aimed at evaluating the effect of menstruation, pregnancy and menopause on salivary flow rate, pH and gustatory function. The study was carried out on 120 patients including 30 controls (with normal menstrual cycle of 28 to 30 d) and 90 cases (30 patients within three days of menstruation, 30 pregnant and 30 postmenopausal). Paraffin-stimulated saliva samples were obtained by expectoration to calculate salivary flow rate, pH was measured electrometically and patients were prospectively evaluated for gustatory function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. No statistically significant difference was found between the groups with respect to salivary flow rate but pH values were significantly lower in post menopausal women (pwomen than intensity of taste perception for other tastes (pwomen reported change in their dietary habits as all of them expressed liking for sweeter food. Reduced salivary flow rate and pH in postmen-opausal women may make them more prone to the occurrence of oral health problems. Also, pregnant and postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between the subjects.

Managing menstruation in the workplace: an overlooked issue in low- and middle-income countries.

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Sommer, Marni; Chandraratna, Sahani; Cavill, Sue; Mahon, Therese; Phillips-Howard, Penelope

2016-06-06

The potential menstrual hygiene management barriers faced by adolescent girls and women in workplace environments in low- and middle-income countries has been under addressed in research, programming and policy. Despite global efforts to reduce poverty among women in such contexts, there has been insufficient attention to the water and sanitation related barriers, specifically in relation to managing monthly menstruation, that may hinder girls' and women's contributions to the workplace, and their health and wellbeing. There is an urgent need to document the specific social and environmental barriers they may be facing in relation to menstrual management, to conduct a costing of the implications of inadequate supportive workplace environments for menstrual hygiene management, and to understand the implications for girls' and women's health and wellbeing. This will provide essential evidence for guiding national policy makers, the private sector, donors and activists focused on advancing girls' and women's rights.

Lipopolysaccharides of Rhizobium etli strain G12 act in potato roots as an inducing agent of systemic resistance to infection by the cyst nematode Globodera pallida.

Science.gov (United States)

Reitz, M; Rudolph, K; Schröder, I; Hoffmann-Hergarten, S; Hallmann, J; Sikora, R A

2000-08-01

Recent studies have shown that living and heat-killed cells of the rhizobacterium Rhizobium etli strain G12 induce in potato roots systemic resistance to infection by the potato cyst nematode Globodera pallida. To better understand the mechanisms of induced resistance, we focused on identifying the inducing agent. Since heat-stable bacterial surface carbohydrates such as exopolysaccharides (EPS) and lipopolysaccharides (LPS) are essential for recognition in the symbiotic interaction between Rhizobium and legumes, their role in the R. etli-potato interaction was studied. EPS and LPS were extracted from bacterial cultures, applied to potato roots, and tested for activity as an inducer of plant resistance to the plant-parasitic nematode. Whereas EPS did not affect G. pallida infection, LPS reduced nematode infection significantly in concentrations as low as 1 and 0.1 mg ml(-1). Split-root experiments, guaranteeing a spatial separation of inducing agent and challenging pathogen, showed that soil treatments of one half of the root system with LPS resulted in a highly significant (up to 37%) systemic induced reduction of G. pallida infection of potato roots in the other half. The results clearly showed that LPS of R. etli G12 act as the inducing agent of systemic resistance in potato roots.

Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation.

Science.gov (United States)

Yao, Dong; Wang, Zheng; Miao, Li; Wang, Linyan

2016-09-15

Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Safflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet

Agent Model Development for Assessing Climate-Induced Geopolitical Instability.

Energy Technology Data Exchange (ETDEWEB)

Boslough, Mark B.; Backus, George A.

2005-12-01

We present the initial stages of development of new agent-based computational methods to generate and test hypotheses about linkages between environmental change and international instability. This report summarizes the first year's effort of an originally proposed three-year Laboratory Directed Research and Development (LDRD) project. The preliminary work focused on a set of simple agent-based models and benefited from lessons learned in previous related projects and case studies of human response to climate change and environmental scarcity. Our approach was to define a qualitative model using extremely simple cellular agent models akin to Lovelock's Daisyworld and Schelling's segregation model. Such models do not require significant computing resources, and users can modify behavior rules to gain insights. One of the difficulties in agent-based modeling is finding the right balance between model simplicity and real-world representation. Our approach was to keep agent behaviors as simple as possible during the development stage (described herein) and to ground them with a realistic geospatial Earth system model in subsequent years. This work is directed toward incorporating projected climate data--including various C02 scenarios from the Intergovernmental Panel on Climate Change (IPCC) Third Assessment Report--and ultimately toward coupling a useful agent-based model to a general circulation model.3

(+)-Grandifloracin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death.

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Ueda, Jun-ya; Athikomkulchai, Sirivan; Miyatake, Ryuta; Saiki, Ikuo; Esumi, Hiroyasu; Awale, Suresh

2014-01-01

Human pancreatic tumors are known to be highly resistant to nutrient starvation, and this prolongs their survival in the hypovascular (austere) tumor microenvironment. Agents that retard this tolerance to nutrient starvation represent a novel antiausterity strategy in anticancer drug discovery. (+)-Grandifloracin (GF), isolated from Uvaria dac, has shown preferential toxicity to PANC-1 human pancreatic cancer cells under nutrient starvation, with a PC50 value of 14.5 μM. However, the underlying mechanism is not clear. In this study, GF was found to preferentially induce PANC-1 cell death in a nutrient-deprived medium via hyperactivation of autophagy, as evidenced by a dramatic upregulation of microtubule-associated protein 1 light chain 3. No change was observed in expression of the caspase-3 and Bcl-2 apoptosis marker proteins. GF was also found to strongly inhibit the activation of Akt, a key regulator of cancer cell survival and proliferation. Because pancreatic tumors are highly resistant to current therapies that induce apoptosis, the alternative cell death mechanism exhibited by GF provides a novel therapeutic insight into antiausterity drug candidates.

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKK? inhibition

OpenAIRE

Tse, Anfernee Kai-Wing; Chen, Ying-Jie; Fu, Xiu-Qiong; Su, Tao; Li, Ting; Guo, Hui; Zhu, Pei-Li; Kwan, Hiu-Yee; Cheng, Brian Chi-Yan; Cao, Hui-Hui; Lee, Sally Kin-Wah; Fong, Wang-Fun; Yu, Zhi-Ling

2017-01-01

Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Eleva...

Ideologies of sexuality, menstruation and risk: girls' experiences of puberty and schooling in northern Tanzania.

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Sommer, Marni

2009-05-01

This paper examines girls' voiced experiences of menstruation, puberty and schooling in northern Tanzania. The study was conducted in Moshi and Rombo Districts of Kilimanjaro, a predominantly Chagga region with historically strong support for girls' education. The major question explored was how the onset of menses and puberty may be impacting on girls' school participation, given societal implications of pubertal onset and potentially gender discriminatory school environments. The methodology included a comparative case study using in-depth interviews and participatory research with young women living in urban and rural Kilimanjaro. Along with important findings about how menstrual onset creates challenges for girls attending school emerged findings about the significant gaps in girls' knowledge about body changes, sexual health and HIV/AIDS. These findings underline the importance of identifying new girl-centred approaches to guidance on bodily development and HIV prevention.

Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

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Lamiaa A Ahmed

Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

The Level of Testosterone, Vitamin D, and Irregular Menstruation More Important than Omega-3 in Non-Symptomatic Women Will Define the Fate of Multiple Scleroses in Future.

Science.gov (United States)

Tavakol, Shima; Shakibapour, Sahar; Bidgoli, Sepideh Arbabi

2018-01-01

Multiple sclerosis is one of the most salient degenerative disorders of CNS with dysregulated immune process that resulted in axonal damage and demyelination. In the present investigation, the serum level of testosterone was assessed in women who were struggling with multiple sclerosis (MS). Also, the level of omega-3, vitamin D, and the irregular menstruation in women 5 years before the onset MS symptoms were surveyed. Although the levels of omega-3 and vitamin D in women MS patients were non-significant and significantly less than the healthy ones, they were significantly less in the whole population of MS patients. However, the MS patients more experienced more irregular menstruation some years before the onset of MS with the low level of testosterone. Based on the presented findings, it might be said that the vitamin D intake has significant protective role in women and men MS patients unlike the omega-3 that had significant protective role just in men. However, vitamin D metabolism encoding genes of CYP27B1 and CYP24A1 and predicting MS risk gene of HLA-DRB1*15:01 define its fate as well. Besides, vitamin D intake, through the proliferation decrement of pro-inflammatory cells, decreases of pro-inflammatory markers (IL-6, TNF-α, INF-γ) and auto-immune pathways have potential role in recovery of irregular menstruation in women with the low level of testosterone as a red warning factor of MS development. The low level of testosterone and vitamin D consumption increase the neural damage and pro-inflammatory pathways in MS patients, and the difference among the investigations is related to the long-standing history of MS that influences severity of damage to the neural cells and biomolecules and complicate its recovery.

'We keep it secret so no one should know'--a qualitative study to explore young schoolgirls attitudes and experiences with menstruation in rural western Kenya.

Directory of Open Access Journals (Sweden)

Linda Mason

Full Text Available BACKGROUND: Keeping girls in school offers them protection against early marriage, teen pregnancy, and sexual harms, and enhances social and economic equity. Studies report menstruation exacerbates school-drop out and poor attendance, although evidence is sparse. This study qualitatively examines the menstrual experiences of young adolescent schoolgirls. METHODS AND FINDINGS: The study was conducted in Siaya County in rural western Kenya. A sample of 120 girls aged 14-16 years took part in 11 focus group discussions, which were analysed thematically. The data gathered were supplemented by information from six FGDs with parents and community members. Emergent themes were: lack of preparation for menarche; maturation and sexual vulnerability; menstruation as an illness; secrecy, fear and shame of leaking; coping with inadequate alternatives; paying for pads with sex; and problems with menstrual hygiene. Girls were unprepared and demonstrated poor reproductive knowledge, but devised practical methods to cope with menstrual difficulties, often alone. Parental and school support of menstrual needs is limited, and information sparse or inaccurate. Girls' physical changes prompt boys and adults to target and brand girls as ripe for sexual activity including coercion and marriage. Girls admitted 'others' rather than themselves were absent from school during menstruation, due to physical symptoms or inadequate sanitary protection. They described difficulties engaging in class, due to fear of smelling and leakage, and subsequent teasing. Sanitary pads were valued but resource and time constraints result in prolonged use causing chafing. Improvised alternatives, including rags and grass, were prone to leak, caused soreness, and were perceived as harmful. Girls reported 'other girls' but not themselves participated in transactional sex to buy pads, and received pads from boyfriends. CONCLUSIONS: In the absence of parental and school support, girls cope

Inducing fluorescence of uranyl acetate as a dual-purpose contrast agent for correlative light-electron microscopy with nanometre precision.

Science.gov (United States)

Tuijtel, Maarten W; Mulder, Aat A; Posthuma, Clara C; van der Hoeven, Barbara; Koster, Abraham J; Bárcena, Montserrat; Faas, Frank G A; Sharp, Thomas H

2017-09-05

Correlative light-electron microscopy (CLEM) combines the high spatial resolution of transmission electron microscopy (TEM) with the capability of fluorescence light microscopy (FLM) to locate rare or transient cellular events within a large field of view. CLEM is therefore a powerful technique to study cellular processes. Aligning images derived from both imaging modalities is a prerequisite to correlate the two microscopy data sets, and poor alignment can limit interpretability of the data. Here, we describe how uranyl acetate, a commonly-used contrast agent for TEM, can be induced to fluoresce brightly at cryogenic temperatures (-195 °C) and imaged by cryoFLM using standard filter sets. This dual-purpose contrast agent can be used as a general tool for CLEM, whereby the equivalent staining allows direct correlation between fluorescence and TEM images. We demonstrate the potential of this approach by performing multi-colour CLEM of cells containing equine arteritis virus proteins tagged with either green- or red-fluorescent protein, and achieve high-precision localization of virus-induced intracellular membrane modifications. Using uranyl acetate as a dual-purpose contrast agent, we achieve an image alignment precision of ~30 nm, twice as accurate as when using fiducial beads, which will be essential for combining TEM with the evolving field of super-resolution light microscopy.

Comparative Evaluation of the Effect of Menstruation, Pregnancy and Menopause on Salivary Flow Rate, pH and Gustatory Function

Science.gov (United States)

Shetty, Vishwaprakash; Dave, Aparna; Arora, Manpreet; Hans, Vibha; Madan, Ajay

2014-01-01

Objective: There are five situations in a women’s life during which hormone fluctuations make them more susceptible to oral health problems – during puberty, at certain points in the monthly menstrual cycle, when using birth control pills, during pregnancy, and at menopause. The present study aimed at evaluating the effect of menstruation, pregnancy and menopause on salivary flow rate, pH and gustatory function. Materials and Methods: The study was carried out on 120 patients including 30 controls (with normal menstrual cycle of 28 to 30 d) and 90 cases (30 patients within three days of menstruation, 30 pregnant and 30 postmenopausal). Paraffin-stimulated saliva samples were obtained by expectoration to calculate salivary flow rate, pH was measured electrometically and patients were prospectively evaluated for gustatory function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. Results: No statistically significant difference was found between the groups with respect to salivary flow rate but pH values were significantly lower in post menopausal women (pwomen than intensity of taste perception for other tastes (pwomen reported change in their dietary habits as all of them expressed liking for sweeter food. Conclusion: Reduced salivary flow rate and pH in postmen­opausal women may make them more prone to the occurrence of oral health problems. Also, pregnant and postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between the subjects. PMID:25478455

Acute Kidney Injury due to Menstruation-related Disseminated Intravascular Coagulation in an Adenomyosis Patient: A Case Report

Science.gov (United States)

Son, Jungmin; Seong, Eun Young; Song, Sang Heon; Lee, Soo Bong; Kang, Jin; Yang, Byeong Yun; Lee, Su Jin; Choi, Jong-Ryeol; Lee, Kyu-Sup; Kwak, Ihm Soo

2010-01-01

The authors report a case of acute kidney injury (AKI) resulting from menstruation-related disseminated intravascular coagulation (DIC) in an adenomyosis patient. A 40-yr-old woman who had received gonadotropin for ovulation induction therapy presented with anuria and an elevated serum creatinine level. Her medical history showed primary infertility with diffuse adenomyosis. On admission, her pregnancy test was negative and her menstrual cycle had started 1 day previously. Laboratory data were consistent with DIC, and it was believed to be related to myometrial injury resulting from heavy intramyometrial menstrual flow. Gonadotropin is considered to play an important role in the development of fulminant DIC. This rare case suggests that physicians should be aware that gonadotropin may provoke fulminant DIC in women with adenomyosis. PMID:20808684

Laser-based instrumentation for the detection of chemical agents

International Nuclear Information System (INIS)

Hartford, A. Jr.; Sander, R.K.; Quigley, G.P.; Radziemski, L.J.; Cremers, D.A.

1982-01-01

Several laser-based techniques are being evaluated for the remote, point, and surface detection of chemical agents. Among the methods under investigation are optoacoustic spectroscopy, laser-induced breakdown spectroscopy (LIBS), and synchronous detection of laser-induced fluorescence (SDLIF). Optoacoustic detection has already been shown to be capable of extremely sensitive point detection. Its application to remote sensing of chemical agents is currently being evaluated. Atomic emission from the region of a laser-generated plasma has been used to identify the characteristic elements contained in nerve (P and F) and blister (S and Cl) agents. Employing this LIBS approach, detection of chemical agent simulants dispersed in air and adsorbed on a variety of surfaces has been achieved. Synchronous detection of laser-induced fluorescence provides an attractive alternative to conventional LIF, in that an artificial narrowing of the fluorescence emission is obtained. The application of this technique to chemical agent simulants has been successfully demonstrated. 19 figures

Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice

Science.gov (United States)

Ahmed, Lamiaa A.; Shehata, Nagwa I.; Abdelkader, Noha F.; Khattab, Mahmoud M.

2014-01-01

Background Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice. Methods and Findings Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I–IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma. Conclusion This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction

De Novo Assembly and Transcriptome Analysis of Wheat with Male Sterility Induced by the Chemical Hybridizing Agent SQ-1.

Directory of Open Access Journals (Sweden)

Qidi Zhu

Full Text Available Wheat (Triticum aestivum L., one of the world's most important food crops, is a strictly autogamous (self-pollinating species with exclusively perfect flowers. Male sterility induced by chemical hybridizing agents has increasingly attracted attention as a tool for hybrid seed production in wheat; however, the molecular mechanisms of male sterility induced by the agent SQ-1 remain poorly understood due to limited whole transcriptome data. Therefore, a comparative analysis of wheat anther transcriptomes for male fertile wheat and SQ-1-induced male sterile wheat was carried out using next-generation sequencing technology. In all, 42,634,123 sequence reads were generated and were assembled into 82,356 high-quality unigenes with an average length of 724 bp. Of these, 1,088 unigenes were significantly differentially expressed in the fertile and sterile wheat anthers, including 643 up-regulated unigenes and 445 down-regulated unigenes. The differentially expressed unigenes with functional annotations were mapped onto 60 pathways using the Kyoto Encyclopedia of Genes and Genomes database. They were mainly involved in coding for the components of ribosomes, photosynthesis, respiration, purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, RNA transport and signal transduction, reactive oxygen species metabolism, mRNA surveillance pathways, protein processing in the endoplasmic reticulum, protein export, and ubiquitin-mediated proteolysis. This study is the first to provide a systematic overview comparing wheat anther transcriptomes of male fertile wheat with those of SQ-1-induced male sterile wheat and is a valuable source of data for future research in SQ-1-induced wheat male sterility.

Neuroprotection for Nerve Agent-Induced Brain Damage

National Research Council Canada - National Science Library

Newmark, Jonathan; Ballough, Gerald P; Filbert, Margaret G

2002-01-01

... secondary to exposure to nerve agents. Preliminary work in this laboratory has demonstrated proof of concept using a compound not yet approved for clinical use by the US Food and Drug Administration...

Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury

International Nuclear Information System (INIS)

Milatovic, Dejan; Gupta, Ramesh C.; Yu, Yingchun; Zaja-Milatovic, Snjezana; Aschner, Michael

2011-01-01

Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (p 2 -isoprostanes (F 2 -IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 μM) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F 2 -IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 μg/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F 2 -IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional dopaminergic transmission and slowing of the progression of Mn-induced neurodegenerative

Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

Science.gov (United States)

Wang, Shuping; Zhang, Gaisheng; Song, Qilu; Zhang, Yingxin; Li, Zheng; Guo, Jialin; Niu, Na; Ma, Shoucai; Wang, Junwei

2015-01-01

Chemical hybridization agent (CHA)-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL) assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD), which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining) were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

Abnormal development of tapetum and microspores induced by chemical hybridization agent SQ-1 in wheat.

Directory of Open Access Journals (Sweden)

Shuping Wang

Full Text Available Chemical hybridization agent (CHA-induced male sterility is an important tool in crop heterosis. To demonstrate that CHA-SQ-1-induced male sterility is associated with abnormal tapetal and microspore development, the cytology of CHA-SQ-1-treated plant anthers at various developmental stages was studied by light microscopy, scanning and transmission electron microscopy, in situ terminal deoxynucleotidyl transferasemediated dUTP nick end-labelling (TUNEL assay and DAPI staining. The results indicated that the SQ-1-treated plants underwent premature tapetal programmed cell death (PCD, which was initiated at the early-uninucleate stage of microspore development and continued until the tapetal cells were completely degraded; the process of microspore development was then blocked. Microspores with low-viability (fluorescein diacetate staining were aborted. The study suggests that premature tapetal PCD is the main cause of pollen abortion. Furthermore, it determines the starting period and a key factor in CHA-SQ-1-induced male sterility at the cell level, and provides cytological evidence to further study the mechanism between PCD and male sterility.

DNA Damage Induced by Alkylating Agents and Repair Pathways

Science.gov (United States)

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

The effect of menstruation on chosen physiological and biochemical reactions caused by the physical effort with the submaximal intensity

Directory of Open Access Journals (Sweden)

P Zieliński

2003-03-01

Full Text Available The aim of this work was to determine the influence of the menstruation phase on changes of respective indicators of the gas exchange and on biochemical parameters of blood during physical efforts with the sub-maximal intensity. Fifteen female students of the Academy of Physical Education took part in the study. Girls were aged from 19 to 22 years old and did not practice sports. The effort tests were conducted in the follicular and luteal phase of two succeeding menstrual cycles. As far the aerobic capacity determination is concerned, one cyclo-ergometric test with graded effort was conducted and it was performed till the “refusal”. It allowed to mark a threshold (TDMA and a maximal level of physiological and biochemical indicators. Basing on the results of the graded test individual loads were determined for every next effort trial (repeated 4 times in every phase of the two succeeding menstrual cycles. The aim of this trial was to evaluate the reaction of women’s constitution on work with the sub-maximal intensity. The above trial consisted on two 10 min efforts divided with the 2 min pause (the first effort with the intensity of 80% of the TDMA threshold, second with the intensity bigger about 30-40% of difference between TDMA and a maximal load established by the graded test. The research did not reveal statistically significant differentiation as considering effort changes of basic physiological and biochemical indicators, determining reaction of women’s organisms on work with the sub- and over- threshold intensity (TDMA. It showed that menstruation has not significant effect on the level of changes of analysed parameters caused by the physical effort with the sub-maximal intensity.

[Experimental testing of Pflüger's reflex hypothesis of menstruation in late 19th century].

Science.gov (United States)

Simmer, H H

1980-07-01

Pflüger's hypothesis of a nerve reflex as the cause of menstruation published in 1865 and accepted by many, nonetheless did not lead to experimental investigations for 25 years. According to this hypothesis the nerve reflex starts in the ovary by an increase of the intraovarian pressure by the growing follicles. In 1884 Adolph Kehrer proposed a program to test the nerve reflex, but only in 1890, Cohnstein artificially increased the intraovarian pressure in women by bimanual compression from the outside and the vagina. His results were not convincing. Six years later, Strassmann injected fluids into ovaries of animals and obtained changes in the uterus resembling those of oestrus. His results seemed to verify a prognosis derived from Pflüger's hypothesis. Thus, after a long interval, that hypothesis had become a paradigma. Though reasons can be given for the delay, it is little understood, why experimental testing started so late.

‘We Keep It Secret So No One Should Know’ – A Qualitative Study to Explore Young Schoolgirls Attitudes and Experiences with Menstruation in Rural Western Kenya

Science.gov (United States)

Mason, Linda; Nyothach, Elizabeth; Alexander, Kelly; Odhiambo, Frank O.; Eleveld, Alie; Vulule, John; Rheingans, Richard; Laserson, Kayla F.; Mohammed, Aisha; Phillips-Howard, Penelope A.

2013-01-01

Background Keeping girls in school offers them protection against early marriage, teen pregnancy, and sexual harms, and enhances social and economic equity. Studies report menstruation exacerbates school-drop out and poor attendance, although evidence is sparse. This study qualitatively examines the menstrual experiences of young adolescent schoolgirls. Methods and Findings The study was conducted in Siaya County in rural western Kenya. A sample of 120 girls aged 14–16 years took part in 11 focus group discussions, which were analysed thematically. The data gathered were supplemented by information from six FGDs with parents and community members. Emergent themes were: lack of preparation for menarche; maturation and sexual vulnerability; menstruation as an illness; secrecy, fear and shame of leaking; coping with inadequate alternatives; paying for pads with sex; and problems with menstrual hygiene. Girls were unprepared and demonstrated poor reproductive knowledge, but devised practical methods to cope with menstrual difficulties, often alone. Parental and school support of menstrual needs is limited, and information sparse or inaccurate. Girls’ physical changes prompt boys and adults to target and brand girls as ripe for sexual activity including coercion and marriage. Girls admitted ‘others’ rather than themselves were absent from school during menstruation, due to physical symptoms or inadequate sanitary protection. They described difficulties engaging in class, due to fear of smelling and leakage, and subsequent teasing. Sanitary pads were valued but resource and time constraints result in prolonged use causing chafing. Improvised alternatives, including rags and grass, were prone to leak, caused soreness, and were perceived as harmful. Girls reported ‘other girls’ but not themselves participated in transactional sex to buy pads, and received pads from boyfriends. Conclusions In the absence of parental and school support, girls cope, sometimes

The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

Science.gov (United States)

Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

2009-01-01

Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

Epidemic spreading induced by diversity of agents' mobility.

Science.gov (United States)

Zhou, Jie; Chung, Ning Ning; Chew, Lock Yue; Lai, Choy Heng

2012-08-01

In this paper, we study the impact of the preference of an individual for public transport on the spread of infectious disease, through a quantity known as the public mobility. Our theoretical and numerical results based on a constructed model reveal that if the average public mobility of the agents is fixed, an increase in the diversity of the agents' public mobility reduces the epidemic threshold, beyond which an enhancement in the rate of infection is observed. Our findings provide an approach to improve the resistance of a society against infectious disease, while preserving the utilization rate of the public transportation system.

Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression

Directory of Open Access Journals (Sweden)

Currie Margaret J

2006-12-01

Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

Effects of inhibitors of DNA repair on the frequencies of chromosomal aberrations induced by x-rays or alkylating agents in cultured human lymphocytes

International Nuclear Information System (INIS)

Kihlman, B.A.; Andersson, H.C.

1986-01-01

In the first part of this presentation the authors give examples of the synergistic enhancements that are obtained with various inhibitor combinations in G/sub 2/. The second part of the presentation deals with the effects of two agents, also well known for their capacity to potentiate the frequency of chromosomal aberrations induced by physical and chemical agents, but with a different mechanism of action. These agents are caffeine and 3-aminobenzamide (3AB). Caffeine has for decades been used as an inhibitor of DNA repair although its mechanism of action has not been fully understood. 3AB has more recently come into focus as an efficient inhibitor of the synthesis of poly-(ADP-ribose), a substance believed to be of importance in connection with the repair of certain types of DNA damage. The results presented do not quite fit in with the general idea about the mode of action of these agents. All experiments were carried out with whole-blood cultures of human lymphocytes. When inhibitors were used as post-treatments, chromosomal aberrations were induced by X-rays or by the alkylating agents thiotepa (TT) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). X-rays were generated by a Siemens Stabilipan 200 apparatus, at a dose rate of 0.5 Gy/min. The tube (TR 200f) was operated at 180 kV, 10 mA and the radiation filtered through 4 mm Al

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Thys, Ryan G., E-mail: rthys@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Lehman, Christine E., E-mail: clehman@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Pierce, Levi C.T., E-mail: Levipierce@gmail.com [Human Longevity, Inc., San Diego, California 92121 (United States); Wang, Yuh-Hwa, E-mail: yw4b@virginia.edu [Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908-0733 (United States)

2015-09-15

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

International Nuclear Information System (INIS)

Thys, Ryan G.; Lehman, Christine E.; Pierce, Levi C.T.; Wang, Yuh-Hwa

2015-01-01

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

Multi Agent System Based Wide Area Protection against Cascading Events

DEFF Research Database (Denmark)

Liu, Zhou; Chen, Zhe; Liu, Leo

2012-01-01

In this paper, a multi-agent system based wide area protection scheme is proposed in order to prevent long term voltage instability induced cascading events. The distributed relays and controllers work as a device agent which not only executes the normal function automatically but also can...... the effectiveness of proposed protection strategy. The simulation results indicate that the proposed multi agent control system can effectively coordinate the distributed relays and controllers to prevent the long term voltage instability induced cascading events....

Complex responses to alkylating agents

International Nuclear Information System (INIS)

Samson, L.D.

2003-01-01

Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

Macroeconomic Policies and Agent Heterogeneity

OpenAIRE

GOTTLIEB, Charles

2012-01-01

Defence date: 24 February 2012 Examining Board: Giancarlo Corsetti, Arpad Abraham, Juan Carlos Conesa, Jonathan Heathcote. This thesis contributes to the understanding of macroeconomic policies’ impact on the distribution of wealth. It belongs to the strand of literature that departs from the representative agent assumption and perceives agent heterogeneity and the induced disparities in wealth accumulation, as an important dimension of economic policy-making. Within such economic envir...

Retrospective analysis of non-laboratory-based adverse drug reactions induced by intravenous radiocontrast agents in a Joint Commission International-accredited academic medical center hospital in China

Directory of Open Access Journals (Sweden)

Chen QL

2017-04-01

Full Text Available Qin-lan Chen,1 Xiao-ying Zhao,2 Xiao-mi Wang,1 Na Lv,2 Ling-ling Zhu,3 Hui-min Xu,4 Quan Zhou4 1Radiology Nursing Unit, Division of Nursing, 2Department of Quality Management, 3Geriatric VIP Care Ward, Division of Nursing, 4Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: The authors retrospectively analyzed the pattern and characteristics of non-laboratory-based adverse drug reactions (ADRs induced by intravenous radiocontrast agents in a large-scale hospital in China during 2014–2015. There were 314 ADR cases among 118,208 patients receiving enhanced CT or MRI examinations. The frequency of moderate/severe ADRs defined by Chinese Society of Radiology (ie, severe vomiting, systematic urticaria, facial swelling, dyspnea, vasovagal reaction, laryngeal edema, seizure, trembling, convulsions, unconsciousness, shock, death, and other unexpected adverse reactions was rare (0.0431%, whereas the mild ADRs were uncommon (0.2225% and accounted for 83.76% of ADRs. Frequency of ADRs induced by iodinated contrast agents was related with examination site, sex, and type of patient settings (P<0.01 and was higher compared with gadolinium contrast agents (0.3676% vs 0.0504%, P<0.01. From 2014 to 2015, frequencies of total and moderate/severe ADRs induced by iodinated contrast agents decreased significantly (0.4410% vs 0.2947%, P<0.01; 0.0960% vs 0.0282%, P<0.01, respectively. Frequency of ADRs differed among different iodinated contrast and gadolinium contrast (P<0.05 agents. Iopromide’s ADR frequency in 2014 was significantly higher compared with iopamidol, ioversol, or iohexol (P<0.01. Frequency of moderate/severe ADRs induced by iodixanol was 4.1–5.4 times that of iohexol, iopromide, or iopamidol. Rash was the predominant ADR subtype (84.39% and occurred more frequently with iodixanol compared with iohexol, iopamidol, or ioversol (P<0

Learning from induced changes in opponent (re)actions in multi-agent games

NARCIS (Netherlands)

P.J. 't Hoen (Pieter Jan); S.M. Bohte (Sander); J.A. La Poutré (Han)

2005-01-01

textabstractMulti-agent learning is a growing area of research. An important topic is to formulate how an agent can learn a good policy in the face of adaptive, competitive opponents. Most research has focused on extensions of single agent learning techniques originally designed for agents in more

Alkylating agent methyl methanesulfonate (MMS) induces a wave of global protein hyperacetylation: Implications in cancer cell death

International Nuclear Information System (INIS)

Lee, Min-Young; Kim, Myoung-Ae; Kim, Hyun-Ju; Bae, Yoe-Sik; Park, Joo-In; Kwak, Jong-Young; Chung, Jay H.; Yun, Jeanho

2007-01-01

Protein acetylation modification has been implicated in many cellular processes but the direct evidence for the involvement of protein acetylation in signal transduction is very limited. In the present study, we found that an alkylating agent methyl methanesulfonate (MMS) induces a robust and reversible hyperacetylation of both cytoplasmic and nuclear proteins during the early phase of the cellular response to MMS. Notably, the acetylation level upon MMS treatment was strongly correlated with the susceptibility of cancer cells, and the enhancement of MMS-induced acetylation by histone deacetylase (HDAC) inhibitors was shown to increase the cellular susceptibility. These results suggest protein acetylation is important for the cell death signal transduction pathway and indicate that the use of HDAC inhibitors for the treatment of cancer is relevant

The Paracrine Induction of TRAIL by Genotoxic Agents

National Research Council Canada - National Science Library

Spalding, Aaron

2002-01-01

TNF related apoptosis inducing ligand, TRAIL, is a recently cloned cytokine that has been shown to induce apoptosis in a synergistic fashion with chemotherapeutic agents on several cancer cell lines...

Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury

Energy Technology Data Exchange (ETDEWEB)

Milatovic, Dejan, E-mail: dejan.milatovic@vanderbilt.edu [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Gupta, Ramesh C. [Murray State University, Breathitt Veterinary Center, Hopkinsville, KY (United States); Yu, Yingchun; Zaja-Milatovic, Snjezana [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Aschner, Michael [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Pharmacology and the Kennedy Center for Research on Human Development, Nashville, TN (United States)

2011-11-15

Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (p < 0.01) increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 {mu}M) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F{sub 2}-IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 {mu}g/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F{sub 2}-IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition

Directory of Open Access Journals (Sweden)

Anfernee Kai-Wing Tse

2017-04-01

Full Text Available Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKβ inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy.

DNA Damage Induced by Alkylating Agents and Repair Pathways

OpenAIRE

Natsuko Kondo; Akihisa Takahashi; Koji Ono; Takeo Ohnishi

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O 6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O 6-methylguanine-DNA methyltransferase, and O 6MeG:T mispairs are recognized...

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

Science.gov (United States)

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-07-09

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53.

Directory of Open Access Journals (Sweden)

Steven N Reuland

Full Text Available Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted.

Ristocetin induces phosphorylated-HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti-platelet agent-effect on the release.

Science.gov (United States)

Tokuda, Haruhiko; Kuroyanagi, Gen; Onuma, Takashi; Enomoto, Yukiko; Doi, Tomoaki; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

2018-04-01

It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin-induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti-platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated-HSP27 induced by ristocetin in the platelets from a patient of the anti-platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin-stimulated platelets were significantly correlated with the levels of phosphorylated-HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet-derived growth factor-AB (PDGF-AB) secretion stimulated by ristocetin in the anti-platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF-AB secretion stimulated by ADP in the anti-platelet group were lower than those in the control group. These results strongly suggest that anti-platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents.

Directory of Open Access Journals (Sweden)

Ryan J Mailloux

2010-10-01

Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.

Instability of expanded simple tandem repeats is induced in cell culture by a variety of agents: N-Nitroso-N-ethylurea, benzo(a)pyrene, etoposide and okadaic acid

Energy Technology Data Exchange (ETDEWEB)

Polyzos, Aris [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Parfett, Craig [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Healy, Caroline [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Douglas, George R. [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Yauk, Carole L. [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada)]. E-mail: Carole_Yauk@hc-sc.gc.ca

2006-06-25

Expanded simple tandem repeat (ESTR) sequences have proven useful biomarkers to detect genotoxicity in vivo. Their high sensitivity has been used to assess environmentally relevant doses of mutagens such as ionizing radiation, DNA alkylating agents and airborne particulate pollution, for germline mutations in mouse assays. The mutagenic response involves size alteration of these ESTR loci induced by agents causing a variety of cellular damage. The mechanistic aspects of this induced instability remain unclear and have not been studied in detail. Mechanistic knowledge is important to help understand the relevance of increased ESTR mutation frequencies. In this study, we applied a murine cell culture system to examine induced response to four agents exhibiting different modes of toxic action including: N-nitroso-N-ethylurea (ENU), benzo(a)pyrene (BaP), okadaic acid and etoposide at slightly sub-toxic levels. We used single-molecule-polymerase chain reaction (SM-PCR) to assess the relative mutant frequency after 4-week chemical treatments at the Ms6-hm ESTR sequence of cultured C3H/10T1/2 cells (a mouse embryonic cell line). Increased mutation was observed with both 0.64 mM ENU (1.95-fold increase, P < 0.0001), 1 {mu}M benzo(a)pyrene (1.87-fold increase, P = 0.0006) and 3 nM etoposide (1.89-fold increase, P = 0.0003). The putative ESTR mutagen okadaic acid (1.27-fold increase, P = 0.2289), administered at 0.5 nM, did not affect the C3H/10T1/2 Ms6-hm locus. Therefore, agents inducing small and bulky adducts, and indirectly causing strand breaks through inhibition of topoisomerase, caused similar induction of instability at an ESTR locus at matched toxicities. As size spectra for induced mutations were identical, the data indicate that although these chemicals exhibit distinct modes of action, a similar indirect process is influencing ESTR instability. In contrast, a potent tumour promoter that is a kinase inhibitor does not contribute to induced ESTR instability in

Instability of expanded simple tandem repeats is induced in cell culture by a variety of agents: N-Nitroso-N-ethylurea, benzo(a)pyrene, etoposide and okadaic acid

International Nuclear Information System (INIS)

Polyzos, Aris; Parfett, Craig; Healy, Caroline; Douglas, George R.; Yauk, Carole L.

2006-01-01

Expanded simple tandem repeat (ESTR) sequences have proven useful biomarkers to detect genotoxicity in vivo. Their high sensitivity has been used to assess environmentally relevant doses of mutagens such as ionizing radiation, DNA alkylating agents and airborne particulate pollution, for germline mutations in mouse assays. The mutagenic response involves size alteration of these ESTR loci induced by agents causing a variety of cellular damage. The mechanistic aspects of this induced instability remain unclear and have not been studied in detail. Mechanistic knowledge is important to help understand the relevance of increased ESTR mutation frequencies. In this study, we applied a murine cell culture system to examine induced response to four agents exhibiting different modes of toxic action including: N-nitroso-N-ethylurea (ENU), benzo(a)pyrene (BaP), okadaic acid and etoposide at slightly sub-toxic levels. We used single-molecule-polymerase chain reaction (SM-PCR) to assess the relative mutant frequency after 4-week chemical treatments at the Ms6-hm ESTR sequence of cultured C3H/10T1/2 cells (a mouse embryonic cell line). Increased mutation was observed with both 0.64 mM ENU (1.95-fold increase, P < 0.0001), 1 μM benzo(a)pyrene (1.87-fold increase, P = 0.0006) and 3 nM etoposide (1.89-fold increase, P = 0.0003). The putative ESTR mutagen okadaic acid (1.27-fold increase, P = 0.2289), administered at 0.5 nM, did not affect the C3H/10T1/2 Ms6-hm locus. Therefore, agents inducing small and bulky adducts, and indirectly causing strand breaks through inhibition of topoisomerase, caused similar induction of instability at an ESTR locus at matched toxicities. As size spectra for induced mutations were identical, the data indicate that although these chemicals exhibit distinct modes of action, a similar indirect process is influencing ESTR instability. In contrast, a potent tumour promoter that is a kinase inhibitor does not contribute to induced ESTR instability in cell

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition.

Science.gov (United States)

Tse, Anfernee Kai-Wing; Chen, Ying-Jie; Fu, Xiu-Qiong; Su, Tao; Li, Ting; Guo, Hui; Zhu, Pei-Li; Kwan, Hiu-Yee; Cheng, Brian Chi-Yan; Cao, Hui-Hui; Lee, Sally Kin-Wah; Fong, Wang-Fun; Yu, Zhi-Ling

2017-04-01

Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKβ inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.

Science.gov (United States)

Zanotto-Filho, Alfeu; Masamsetti, V Pragathi; Loranc, Eva; Tonapi, Sonal S; Gorthi, Aparna; Bernard, Xavier; Gonçalves, Rosângela Mayer; Moreira, José C F; Chen, Yidong; Bishop, Alexander J R

2016-12-01

Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis, and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. GSH is essential for both drug detoxification and protein thiol homeostasis within the ER, thus inhibiting ER stress induction and promoting survival, an effect independent of its antioxidant role. NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N-acetylcysteine or glutathione-ethyl-ester, decreased ER stress and abrogated alkylating agents-induced cell death. Based on these results, we identified a subset of lung and head-and-neck carcinomas with mutations in either KEAP1 or NRF2/NFE2L2 genes that correlate with NRF2 target overexpression and poor survival. In KEAP1-mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. Mol Cancer Ther; 15(12); 3000-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Alkylating agent induced NRF2 blocks endoplasmic reticulum stress-mediated apoptosis via control of glutathione pools and protein thiol homeostasis

Science.gov (United States)

Zanotto-Filho, Alfeu; Masamsetti, V. Pragathi; Loranc, Eva; Tonapi, Sonal S.; Gorthi, Aparna; Bernard, Xavier; Gonçalves, Rosângela Mayer; Moreira, José C. F.; Chen, Yidong; Bishop, Alexander J. R.

2016-01-01

Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. GSH is essential for both drug detoxification and protein thiol homeostasis within the ER, thus inhibiting ER stress induction and promoting survival; an effect independent of its antioxidant role. NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine (BSO) caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N-acetylcysteine (NAC) or glutathione-ethyl-ester (GSH-E), decreased ER stress and abrogated alkylating agents-induced cell death. Based on these results, we identified a subset of lung and head-and-neck carcinomas with mutations in either KEAP1 or NRF2/NFE2L2 genes that correlate with NRF2 targets overexpression and poor survival. In KEAP1 mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. PMID:27638861

Possible targets for the aneugenic activity of alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Pellerano, P. [IST-National Institute for Research on Cancer, Genova (Italy); Abbondandolo, A. [Univ. of Genova (Italy); Bonatti, S.; Simili, M. [CNR Institute of Mutagenesis and Differentiation, Pisa (Italy)

1993-12-31

Alkylating agents have been of invaluable help in mutation research for half a century. In all tested organisms, they have proved able to induce a large variety of genetic effects, including aneuploidy. Credible molecular models exist to explain the ability of alkylating agents to induce gene mutation and to act as initiators in carcinogenesis as a consequence of DNA alkylation at specific sites. On the contrary, neither the mechanism of aneuploidy induction nor the relevant cellular targets are known.

Contrast agent enhanced pQCT of articular cartilage

Energy Technology Data Exchange (ETDEWEB)

Kallioniemi, A S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Jurvelin, J S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Nieminen, M T [Department of Diagnostic Radiology, POB 50, 90029 OYS, Oulu University Hospital, Oulu (Finland); Lammi, M J [Department of Anatomy, Institute of Biomedicine, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Toeyraes, J [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland)

2007-02-21

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T{sub 1,Gd} and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

Contrast agent enhanced pQCT of articular cartilage

Science.gov (United States)

Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

2007-02-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

Contrast agent enhanced pQCT of articular cartilage

International Nuclear Information System (INIS)

Kallioniemi, A S; Jurvelin, J S; Nieminen, M T; Lammi, M J; Toeyraes, J

2007-01-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T 1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded

Radiation-induced molecular imprinting of D-glucose onto poly(2-hydroxyethyl methacrylate) matrices using various crosslinking agents

International Nuclear Information System (INIS)

Ates, Zeliha; Gueven, Olgun

2010-01-01

Radiation-induced molecular imprinting of D-glucose onto poly(2-hydroxyethyl methacrylate) matrix was achieved to create three-dimensional cavities to recognize and bind D-glucose. The optimization of imprinting capability of matrices was achieved by investigating the effects of various parameters such as the type and amount of crosslinking agent, type of solvent, template to monomer ratio and total absorbed dose. Crosslinking agents with increasing chain lengths and different flexibilities were used in an attempt to elucidate the impact of relevant imprint parameters on the effectiveness of imprinting technique. The absorbed dose varied from 1 to 15 kGy. Cavity sizes of MIPs were measured by positron annihilation lifetime (PAL) experiments. Control matrices were synthesized with exactly the same composition in the absence of D-glucose. Separation of D-glucose has been shown to be successfully achieved in HPLC columns filled with MIPs whereas no separation was observed for non-imprint matrices.

The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302

Science.gov (United States)

2014-11-01

to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the cur- rent US Food and Drug... status epilepticus (SE), which are initiated by the excessive stimulation of cholinergic receptors. If immediate death is prevented by adequate...5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid; PBS, phosphate-buffered saline; SE, status epilepticus ; UBP302, (S)-3-(2-carboxybenzyl

Identification of vapor-phase chemical warfare agent simulants and rocket fuels using laser-induced breakdown spectroscopy

International Nuclear Information System (INIS)

Stearns, Jaime A.; McElman, Sarah E.; Dodd, James A.

2010-01-01

Application of laser-induced breakdown spectroscopy (LIBS) to the identification of security threats is a growing area of research. This work presents LIBS spectra of vapor-phase chemical warfare agent simulants and typical rocket fuels. A large dataset of spectra was acquired using a variety of gas mixtures and background pressures and processed using partial least squares analysis. The five compounds studied were identified with a 99% success rate by the best method. The temporal behavior of the emission lines as a function of chamber pressure and gas mixture was also investigated, revealing some interesting trends that merit further study.

Identification of vapor-phase chemical warfare agent simulants and rocket fuels using laser-induced breakdown spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Stearns, Jaime A.; McElman, Sarah E.; Dodd, James A.

2010-05-01

Application of laser-induced breakdown spectroscopy (LIBS) to the identification of security threats is a growing area of research. This work presents LIBS spectra of vapor-phase chemical warfare agent simulants and typical rocket fuels. A large dataset of spectra was acquired using a variety of gas mixtures and background pressures and processed using partial least squares analysis. The five compounds studied were identified with a 99% success rate by the best method. The temporal behavior of the emission lines as a function of chamber pressure and gas mixture was also investigated, revealing some interesting trends that merit further study.

Galectin-7 is important for normal uterine repair following menstruation.

Science.gov (United States)

Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen

2014-08-01

Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the

Base damage within single-strand DNA underlies in vivo hypermutability induced by a ubiquitous environmental agent.

Directory of Open Access Journals (Sweden)

Kin Chan

Full Text Available Chromosomal DNA must be in single-strand form for important transactions such as replication, transcription, and recombination to occur. The single-strand DNA (ssDNA is more prone to damage than double-strand DNA (dsDNA, due to greater exposure of chemically reactive moieties in the nitrogenous bases. Thus, there can be agents that damage regions of ssDNA in vivo while being inert toward dsDNA. To assess the potential hazard posed by such agents, we devised an ssDNA-specific mutagenesis reporter system in budding yeast. The reporter strains bear the cdc13-1 temperature-sensitive mutation, such that shifting to 37°C results in telomere uncapping and ensuing 5' to 3' enzymatic resection. This exposes the reporter region, containing three closely-spaced reporter genes, as a long 3' ssDNA overhang. We validated the ability of the system to detect mutagenic damage within ssDNA by expressing a modified human single-strand specific cytosine deaminase, APOBEC3G. APOBEC3G induced a high density of substitutions at cytosines in the ssDNA overhang strand, resulting in frequent, simultaneous inactivation of two reporter genes. We then examined the mutagenicity of sulfites, a class of reactive sulfur oxides to which humans are exposed frequently via respiration and food intake. Sulfites, at a concentration similar to that found in some foods, induced a high density of mutations, almost always as substitutions at cytosines in the ssDNA overhang strand, resulting in simultaneous inactivation of at least two reporter genes. Furthermore, sulfites formed a long-lived adducted 2'-deoxyuracil intermediate in DNA that was resistant to excision by uracil-DNA N-glycosylase. This intermediate was bypassed by error-prone translesion DNA synthesis, frequently involving Pol ζ, during repair synthesis. Our results suggest that sulfite-induced lesions in DNA can be particularly deleterious, since cells might not possess the means to repair or bypass such lesions

Risk Stratification of iodine-induced thyrotoxicosis before contrast agent application; Prognosebeurteilung bei geplanter Kontrastmittelexposition

Energy Technology Data Exchange (ETDEWEB)

Fricke, E. [Inst. fuer Molekulare Biophysik, Radiochemie und Nuklearmedizin, Herz- und Diabeteszentrum, Nordrheinwestfalen, Bad Oeynhausen (Germany)

2004-06-01

Today, examinations using iodine containing contrast media are rather frequent. Even though in modern contrast agents the content of free iodine is low, in vivo deiodination results in a non physiologic high iodine load of the thyroid gland. Whilst in normal thyroid tissue iodine metabolism and hormone production are self-regulating in spite of the variable iodine load, those mechanisms are disturbed in autonomous thyroid tissue. Clinical studies displayed low risk of iodine induced thyrotoxicosis after application of contrast agent. Nonetheless the clinician has to assess the risk of thyrotoxicosis for each individual patient and he has to decide how to cope with this risk. Thyroid scintigraphy using Tc-99m-pertechnetate with quantitative measurement of the thyroidal uptake (TcTU) has been shown to be a useful tool in this question, especially when performed under suppression of the non-autonomous tissue (TcTUs). In particular patients with pre-existing suppression of the TSH secretion should be selected for this investigation. Also at risk are elderly persons and those with diffuse or nodular goitres. In spite of the high frequency of contrast agent applications, data on scintigraphy for risk evaluation of thyrotoxicosis and on efficacy of prophylactic medication are scarce. Based on own results and on a review of literature, the risk of thyrotoxicosis seems to be negligible in patients with a TcTUs of less than 1% even in case of preexistent latent hyperthyroidism. If a suppressed TSH level is known and TcTUs is higher than 1%, prophylactic medication should be given. There is evidence for a combination therapy inhibiting both iodine uptake and metabolism, i.e. with perchlorate and thiamazole, being more efficient than monotherapy, particularly in patients with high risk of thyrotoxicosis. (orig.)

Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles.

Science.gov (United States)

Johnson, Lauren; Sammel, Mary D; Schanne, Allison; Lechtenberg, Lara; Prewitt, Maureen; Gracia, Clarisa

2016-12-01

To evaluate reproductive hormone patterns in women exposed to alkylating-agent chemotherapy. Prospective cohort. University hospital. Normally menstruating mid-reproductive-age women (20-35 years old) who had previously been exposed to alkylating-agent chemotherapy for cancer treatment were compared with two healthy control populations: similarly-aged women and late-reproductive-age women (43-50 years old). Subjects collected daily urine samples for one cycle. Integrated urinary pregnanediol glucuronide (PDG) and estrone conjugate (E1c) and urinary excretion of gonadotropins (FSH and LH). Thirty-eight women (13 survivors, 11 same-age control subjects, 14 late-reproductive-age control subjects) provided 1,082 urine samples. Cycle length, luteal phase length, and evidence of luteal activity were similar among the groups. As expected, ovarian reserve was impaired in cancer survivors compared with same-age control subjects but similar between survivors and late-reproductive-age control subjects. In contrast, survivors had total and peak PDG levels that were similar to same-age control subjects and higher than those observed in late-reproductive-age control subjects. Survivors had higher E1c levels than both same-age and late-reproductive-age control subjects. There was no difference in urinary gonadotropins among the groups. Women exposed to alkylating agents have a unique reproductive hormone milieu that is not solely explained by age or ovarian reserve. The urinary hormone profile observed in survivors appears more similar to same-age control subjects than to late-reproductive-age women with similar ovarian reserve, which may suggest that age plays a more important role than ovarian reserve in the follicular dynamics of survivors. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Activity induced phase transition in mixtures of active and passive agents

Science.gov (United States)

Sinha Mahapatra, Pallab; Kulkarni, Ajinkya

2017-11-01

Collective behaviors of self-propelling agents are ubiquitous in nature that produces interesting patterns. The objective of this study is to investigate the phase transition in mixtures of active and inert agents suspended in a liquid. A modified version of the Vicsek Model has been used (see Ref.), where the particles are modeled as soft disks with finite mass, confined in a square domain. The particles are required to align their local motion to their immediate neighborhood, similar to the Vicsek model. We identified the transition from disorganized thermal-like motion to an organized vortical motion. We analyzed the nature of the transition by using different order parameters. Furthermore the switching between the phases has been investigated via artificial nucleation of randomly picked active agents spanning the entire domain. Finally the motivation for this phase transition has been explained via average dissipation and the mean square displacement (MSD) of the agents.

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

Science.gov (United States)

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

[Mining analysis on composition and medication of menstruation prescriptions in Fu Qingzhu's Obstetrics and Gynecology].

Science.gov (United States)

Zhu, Jia-qing; Che, Yu-xia

2015-04-01

In this paper, menstruation prescriptions were selected from "Fu Qingzhu's Obstetrics and Gynecology" and analyzed by using GRI algorithm, correlation analysis, hierarchical clustering method through SPSS, Clementine and traditional Chinese medicine (TCM) inheritance auxiliary systems, in order to screen out 15 menopathy prescriptions, which involve 45 traditional Chinese medicine herbs. In the study, blood-tonifying and qi-tonifying herbs were found to be frequent in the prescriptions. The most frequent single herb was white paeony root, accounting for 9.6% in the total number of prescriptions; The most frequent herb pairs were white paeony root-radix rehmanniae preparata and paeony root-angelica sinensis. Among Fu Shan's menopathy prescriptions, 61 herbal pairs showed a correlation coefficient exceeding 0.05, which evolved into 16 pairs of core combinations. The analysis showed that menopathy prescriptions in volume 1 of "Fu Qingzhu's Obstetrics and Gynecology" focused on tonic traditional Chinese medicines involving liver, spleen and kidney and were adjusted according to changes in qi, blood, cold, hot and wet, which could provide a specific reference for further studies on Fu Shan's academic thoughts and traditional Chinese medicine clinical treatment of menopathy.

Biocontrol agent Bacillus amyloliquefaciens LJ02 induces systemic resistance against cucurbits powdery mildew.

Science.gov (United States)

Li, Yunlong; Gu, Yilin; Li, Juan; Xu, Mingzhu; Wei, Qing; Wang, Yuanhong

2015-01-01

Powdery mildew is a fungal disease found in a wide range of plants and can significantly reduce crop yields. Bacterial strain LJ02 is a biocontrol agent (BCA) isolated from a greenhouse in Tianjin, China. In combination of morphological, physiological, biochemical and phylogenetic analyses, strain LJ02 was classified as a new member of Bacillus amyloliquefaciens. Greenhouse trials showed that LJ02 fermentation broth (LJ02FB) can effectively diminish the occurrence of cucurbits powdery mildew. When treated with LJ02FB, cucumber seedlings produced significantly elevated production of superoxide dismutase, peroxidase, polyphenol oxidase and phenylalanine ammonia lyase as compared to that of the control. We further confirmed that the production of free salicylic acid (SA) and expression of one pathogenesis-related (PR) gene PR-1 in cucumber leaves were markedly elevated after treating with LJ02FB, suggesting that SA-mediated defense response was stimulated. Moreover, LJ02FB-treated cucumber leaves could secrete resistance-related substances into rhizosphere that inhibit the germination of fungi spores and the growth of pathogens. Finally, we separated bacterium and its fermented substances to test their respective effects and found that both components have SA-inducing activity and bacterium plays major roles. Altogether, we identified a BCA against powdery mildew and its mode of action by inducing systemic resistance such as SA signaling pathway.

Ultrasound-induced Gas Release from Contrast Agent Microbubbles

NARCIS (Netherlands)

Postema, M.A.B.; Postema, Michiel; Bouakaz, Ayache; Versluis, Michel; de Jong, N.

2005-01-01

We investigated gas release from two hard-shelled ultrasound contrast agents by subjecting them to high-mechanical index (MI) ultrasound and simultaneously capturing high-speed photographs. At an insonifying frequency of 1.7 MHz, a larger percentage of contrast bubbles is seen to crack than at 0.5

Investigating the influence of social exclusion on persuasion by a virtual agent

NARCIS (Netherlands)

Ruijten, P.A.M.; Ham, J.R.C.; Midden, C.J.H.; Spagnolli, A.; Chittaro, L.; Gamberini, L.

2014-01-01

Persuasive agents may function as a tool to induce changes in human behavior. Research has shown that human-likeness of such agents influences their effectiveness. Besides characteristics of the agent, other characteristics may also have strong influences on persuasive agents’ effectiveness. One

HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress.

Science.gov (United States)

Khanra, Kalyani; Chakraborty, Anindita; Bhattacharyya, Nandan

2015-01-01

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (polβ Δ208-304) specific for ovarian cancer. Pol β Δ208-304 has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. Polβ Δ208-304 cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has been shown that cell death in Pol β Δ208-304 transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

Inciting and etiologic agents of colitis.

Science.gov (United States)

Silva, J; Fekety, R; Werk, C; Ebright, J; Cudmore, M; Batts, D; Syrjamaki, C; Lukens, J

1984-01-01

Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

Optimal Wonderful Life Utility Functions in Multi-Agent Systems

Science.gov (United States)

Wolpert, David H.; Tumer, Kagan; Swanson, Keith (Technical Monitor)

2000-01-01

The mathematics of Collective Intelligence (COINs) is concerned with the design of multi-agent systems so as to optimize an overall global utility function when those systems lack centralized communication and control. Typically in COINs each agent runs a distinct Reinforcement Learning (RL) algorithm, so that much of the design problem reduces to how best to initialize/update each agent's private utility function, as far as the ensuing value of the global utility is concerned. Traditional team game solutions to this problem assign to each agent the global utility as its private utility function. In previous work we used the COIN framework to derive the alternative Wonderful Life Utility (WLU), and experimentally established that having the agents use it induces global utility performance up to orders of magnitude superior to that induced by use of the team game utility. The WLU has a free parameter (the clamping parameter) which we simply set to zero in that previous work. Here we derive the optimal value of the clamping parameter, and demonstrate experimentally that using that optimal value can result in significantly improved performance over that of clamping to zero, over and above the improvement beyond traditional approaches.

Nearest neighbor affects G:C to A:T transitions induced by alkylating agents.

Science.gov (United States)

Glickman, B W; Horsfall, M J; Gordon, A J; Burns, P A

1987-01-01

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference was not seen following treatment with ethylmethanesulfonate. The observed preference for 5'PuG-3' site over 5'-PyG-3' sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells. PMID:3329097

Nearest neighbor affects G:C to A:T transitions induced by alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Glickman, B.W.; Horsfall, M.J.; Gordon, A.J.E.; Burns, P.A.

1987-12-01

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preferences was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species in the alkyl diazonium ion. In contrast, this preferences was not seen following treatment with ethylmethanesulfonate. The observed preference for 5'PuG-3' site over 5'-PyG-3' sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells.

Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

Science.gov (United States)

Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

2016-01-01

Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

Chemical warfare agents identification by thermal neutron detection

International Nuclear Information System (INIS)

Liu Boxue; Ai Xianyun; Tan Daoyuan; Zhang Dianqin

2000-01-01

The hydrogen concentration determination by thermal neutron detection is a non-destructive, fast and effective method to identify chemical warfare agents and TNT that contain different hydrogen fraction. When an isotropic neutron source is used to irradiate chemical ammunition, hydrogen atoms of the agent inside shell act as a moderator and slow down neutrons. The number of induced thermal neutrons depends mainly upon hydrogen content of the agent. Therefore measurement of thermal neutron influence can be used to determine hydrogen atom concentration, thereby to determine the chemical warfare agents. Under a certain geometry three calibration curves of count rate against hydrogen concentration were measured. According to the calibration curves, response of a chemical agent or TNT could be calculated. Differences of count rate among chemical agents and TNT for each kind of shells is greater than five times of standard deviations of count rate for any agent, so chemical agents or TNT could be identified correctly. Meanwhile, blast tube or liquid level of chemical warfare agent could affect the response of thermal neutron count rate, and thereby the result of identification. (author)

Neuromuscular transmission: new concepts and agents.

NARCIS (Netherlands)

Boer, H.D. de

2009-01-01

Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.

Science.gov (United States)

Lee, Bo-Ah; Lee, Hwa-Sun; Jung, Young-Suk; Kim, Se-Won; Lee, Yong-Wook; Chang, Sun-Hwa; Chung, Hyun-Ju; Kim, Ok-Su; Kim, Young-Joon

2013-08-01

The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model. The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P botanical mixture significantly reduced the alveolar bone loss in a rat model (P botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found. The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed

An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation.

Science.gov (United States)

Çatlı, Gönül; Alparslan, Caner; Can, P Şule; Akbay, Sinem; Kelekçi, Sefa; Atik, Tahir; Özyılmaz, Berk; Dündar, Bumin N

2015-06-01

46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.

In Situ Monitoring of RAFT Polymerization by Tetraphenylethylene-Containing Agents with Aggregation-Induced Emission Characteristics.

Science.gov (United States)

Liu, Shunjie; Cheng, Yanhua; Zhang, Haoke; Qiu, Zijie; Kwok, Ryan T K; Lam, Jacky W Y; Tang, Ben Zhong

2018-05-22

A facile and efficient approach is demonstrated to visualize the polymerization in situ. A group of tetraphenylethylene (TPE)-containing dithiocarbamates were synthesized and screened as agents for reversible addition fragmentation chain transfer (RAFT) polymerizations. The spatial-temporal control characteristics of photochemistry enabled the RAFT polymerizations to be ON and OFF on demand under alternating visible light irradiation. The emission of TPE is sensitive to the local viscosity change owing to its aggregation-induced emission characteristic. Quantitative information could be easily acquired by the naked eye without destroying the reaction system. Furthermore, the versatility of such a technique was well demonstrated by 12 different polymerization systems. The present approach thus demonstrated a powerful platform for understanding the controlled living radical polymerization process. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid.

Science.gov (United States)

Bonnar, J; Sheppard, B L

1996-09-07

To compare the efficacy and acceptability of ethamsylate, mefenamic acid, and tranexamic acid for treating menorrhagia. Randomised controlled trial. A university department of obstetrics and gynaecology. 76 women with dysfunctional uterine bleeding. Treatment for five days from day 1 of menses during three consecutive menstrual periods. 27 patients were randomised to take ethamsylate 500 mg six hourly, 23 patients to take mefenamic acid 500 mg eight hourly, and 26 patients to take tranexamic acid 1 g six hourly. Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment; duration of bleeding; patient's estimation of blood loss; sanitary towel usage; the occurrence of dysmenorrhoea; and unwanted events. Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20% (mean blood loss 186 ml before treatment, 148 ml during treatment) and tranexamic acid reduced blood loss by 54% (mean blood loss 164 ml before treatment, 75 ml during treatment). Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid. Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding. Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery.

Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

2013-05-01

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice

Directory of Open Access Journals (Sweden)

Chinthalapally V. Rao

2013-09-01

Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group or 34 weeks (15 mice/group to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001 lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001 lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.

An attempt for clarifying some complications due to induced abortion by means of radioisotopes

International Nuclear Information System (INIS)

Atanasov, A.; Mlychkov, Kh.

1975-01-01

The possibility and degree of tissue and plasmic elements invasion and deportation during induced abortion depending on the operative method used are studied comparatively. To this end before the operation a lavage of the uterine cavity with technecium was performed. Ten minutes later blood radionuclide concentration was measured. A greater radionuclide blood concentration was observed after abortion made after the aspiration method than after abortion by the classical abrasive method. This indicates a greater invasion and deportation of tissue and plasmic elements from the embryo in the mother's blood circulation and is a substantial failure of the aspiration method which accounts for the more frequently occurring protracted menstruation disorders in such cases. (A.B.)

Ultraviolet Raman scattering from persistent chemical warfare agents

Science.gov (United States)

Kullander, Fredrik; Wästerby, Pär.; Landström, Lars

2016-05-01

Laser induced Raman scattering at excitation wavelengths in the middle ultraviolet was examined using a pulsed tunable laser based spectrometer system. Droplets of chemical warfare agents, with a volume of 2 μl, were placed on a silicon surface and irradiated with sequences of laser pulses. The Raman scattering from V-series nerve agents, Tabun (GA) and Mustard gas (HD) was studied with the aim of finding the optimum parameters and the requirements for a detection system. A particular emphasis was put on V-agents that have been previously shown to yield relatively weak Raman scattering in this excitation band.

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

International Nuclear Information System (INIS)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-01-01

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of γ-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of γ-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced γ-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression

Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

Energy Technology Data Exchange (ETDEWEB)

Liu, J.-S.; Kuo, S.-R.; Melendy, Thomas

2003-11-27

To better understand the different cellular responses to replication fork pausing versus blockage, early DNA damage response markers were compared after treatment of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) and adozelesin). These agents were compared for their relative abilities to induce phosphorylation of Chk1, H2AX, and replication protein A (RPA), and intra-nuclear focalization of {gamma}-H2AX and RPA. Treatment by aphidicolin and HU resulted in phosphorylation of Chk1, while HU, but not aphidicolin, induced focalization of {gamma}-H2AX and RPA. Surprisingly, pre-treatment with aphidicolin to stop replication fork progression, did not abrogate HU-induced {gamma}-H2AX and RPA focalization. This suggests that HU may act on the replication fork machinery directly, such that fork progression is not required to trigger these responses. The DNA-damaging fork-blocking agents, adozelesin and MMS, both induced phosphorylation and focalization of H2AX and RPA. Unlike adozelesin and HU, the pattern of MMS-induced RPA focalization did not match the BUdR incorporation pattern and was not blocked by aphidicolin, suggesting that MMS-induced damage is not replication fork-dependent. In support of this, MMS was the only reagent used that did not induce phosphorylation of Chk1. These results indicate that induction of DNA damage checkpoint responses due to adozelesin is both replication fork and fork progression dependent, induction by HU is replication fork dependent but progression independent, while induction by MMS is independent of both replication forks and fork progression.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Directory of Open Access Journals (Sweden)

Thai Q Tran

2017-11-01

Full Text Available Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

Science.gov (United States)

Tran, Thai Q; Ishak Gabra, Mari B; Lowman, Xazmin H; Yang, Ying; Reid, Michael A; Pan, Min; O'Connor, Timothy R; Kong, Mei

2017-11-01

Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents.

Science.gov (United States)

Yadav, N; Kumar, S; Marlowe, T; Chaudhary, A K; Kumar, R; Wang, J; O'Malley, J; Boland, P M; Jayanthi, S; Kumar, T K S; Yadava, N; Chandra, D

2015-11-05

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency

Protection Against Chemical Agent-Induced, Seizure-Related Neuronal Cell Death

National Research Council Canada - National Science Library

Ballough, Gerald P; Filbert, Margaret G

2002-01-01

.... While seizure-related brain damage can be prevented by administration of an anticonvulsant drug, battlefield conditions may preclude prompt administration of the convulsant antidote for nerve agents (CANA...

ACOG Committee Opinion No. 651: Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign.

Science.gov (United States)

2015-12-01

Despite variations worldwide and within the U.S. population, median age at menarche has remained relatively stable-between 12 years and 13 years-across well-nourished populations in developed countries. Environmental factors, including socioeconomic conditions, nutrition, and access to preventive health care, may influence the timing and progression of puberty. A number of medical conditions can cause abnormal uterine bleeding, characterized by unpredictable timing and variable amount of flow. Clinicians should educate girls and their caretakers (eg, parents or guardians) about what to expect of a first menstrual period and the range for normal cycle length of subsequent menses. Identification of abnormal menstrual patterns in adolescence may improve early identification of potential health concerns for adulthood. It is important for clinicians to have an understanding of the menstrual patterns of adolescent girls, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate the adolescent girl patient. By including an evaluation of the menstrual cycle as an additional vital sign, clinicians reinforce its importance in assessing overall health status for patients and caretakers.

Therapeutic and Ethical Dilemma of Puberty and Menstruation Problems in an Intellectually Disabled (Autistic) Female: a Case Report.

Science.gov (United States)

Memarian, Azadeh; Mehrpisheh, Shahrokh

2015-10-01

Intellectual disability is a term used when a person has certain limitations in mental functioning and skills. Autism is a group of developmental brain disorders, collectively called autism spectrum disorder (ASD). Teenagers with learning and physical disabilities are more likely to have menstrual problems compared to the general populations. The parents of a 12-year-old girl with autism spectrum disorder and intellectual disability referred to the coroner due to her numerous problems of puberty (menstruation) including: poor hygiene and polluting herself and the environment, not allowing to put or change the pads and changes in mood and physical health prior period, requested for the surgery (hysterectomy). In legal medicine organization after reviewing the medical records, physical exams and medical consultations with a gynecologist and psychiatric, surgery was not accepted. Hysterectomy (surgery) due to the age of the child, either physically or morally is not recommended. The use of hormone replacement therapy has side effects such as osteoporosis. In these cases, it seems noninvasive methods (behavioral therapy and learning care skills) under the welfare experts is also more effective and morally.

Development of Protective Agent Against Sulfur Mustard-Induced Skin Lesions

National Research Council Canada - National Science Library

Wormser, Uri

2002-01-01

.... Incorporation of the antiinflammatory drug piroxicam and the steroidal antiinflamamtory agent clobetasol, caused the formulation to protect at intervals of 45 and 60 rain in the mouse ear swelling...

Quantification of apoptotic DNA fragmentation in a transformed uterine epithelial cell line, HRE-H9, using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF).

Science.gov (United States)

Fiscus, R R; Leung, C P; Yuen, J P; Chan, H C

2001-01-01

Apoptotic cell death of uterine epithelial cells is thought to play an important role in the onset of menstruation and the successful implantation of an embryo during early pregnancy. Abnormal apoptosis in these cells can result in dysmenorrhoea and infertility. In addition, decreased rate of epithelial apoptosis likely contributes to endometriosis. A key step in the onset of apoptosis in these cells is cleavage of the genomic DNA between nucleosomes, resulting in polynucleosomal-sized fragments of DNA. The conventional technique for assessing apoptotic DNA fragmentation uses agarose (slab) gel electrophoresis (i.e. DNA laddering). However, recent technological advances in the use of capillary electrophoresis (CE), particularly the introduction of the laser-induced fluorescence detector (LIF), has made it possible to perform DNA laddering with improved automation and much greater sensitivity. In the present study, we have further developed the CE-LIF technique by using a DNA standard curve to quantify accurately the amount of DNA in the apoptotic DNA fragments and have applied this new quantitative technique to study apoptosis in a transformed uterine epithelial cell line, the HRE-H9 cells. Apoptosis was induced in the HRE-H9 cells by serum deprivation for 5, 7 and 24 h, resulting in increased DNA fragmentation of 2.2-, 3.1- and 6.2-fold, respectively, above the 0 h or plus-serum controls. This ultrasensitive CE-LIF technique provides a novel method for accurately measuring the actions of pro- or anti-apoptotic agents or conditions on uterine epithelial cell lines. Copyright 2001 Academic Press.

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis.

Science.gov (United States)

Pirdel, Leila; Pirdel, Manijeh

2014-06-01

This article presents an overview of the involvement of iron overload-induced nitric oxide (NO) overproduction in apoptosis of peritoneal macrophages of women with endometriosis. We have postulated that the peritoneal iron overload originated from retrograde menstruation or bleeding lesions in the ectopic endometrium, which may contribute to the development of endometriosis by a wide range of mechanisms, including oxidative damage and chronic inflammation. Excessive NO production may also be associated with impaired clearance of endometrial cells by macrophages, which promotes cell growth in the peritoneal cavity. Therefore, further research of the mechanisms and consequences of macrophage apoptosis in endometriosis helps discover novel therapeutic strategies that are designed to prevent progression of endometriosis. © 2014 Society for Reproduction and Fertility.

Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine

DEFF Research Database (Denmark)

Tepel, Martin; van der Giet, M; Schwarzfeld, C

2000-01-01

Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown.......Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown....

Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination

International Nuclear Information System (INIS)

Radford, I.R.

1986-01-01

The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA lesions are also discussed. (author)

[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].

Science.gov (United States)

Satoh, Jo

2003-07-01

Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.

Plasma lipid peroxidation, blood GSH concentration and erythrocyte antioxidant enzymes in menstruating females with ovulatory and anovulatory cycles compared with males

Directory of Open Access Journals (Sweden)

G Lutosławska

2003-12-01

Full Text Available This study was undertaken to evaluate plasma TBARS and blood GSH concentration and erythrocyte antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase in active, regularly menstruating female physical education students with ovulatory and anovulatory menstrual cycles and in their male counterparts. A total of 27 subjects (12 males and 15 females volunteered to participate in the study. All females were regularly menstruating with cycle length between 26-31 days. Plasma progesterone and 17-β-estradiol concentrations were assayed during the 7th-9th and 22nd-25th day of the menstrual cycle. Women with plasma progesterone concentration exceeding 19 nmol•l-1 during the 22nd-25th day were referred to as ovulatory (Group OV; n=7. Women without a peak plasma progesterone concentration were referred to as anovulatory (Group AN; n=8. Blood from male subjects was withdrawn twice - two weeks apart, at their convenience. It was found that the menstrual cycle phases did not affect plasma TBARS and blood glutathione concentration and erythrocyte GPX, CAT and SOD activity. However, erythrocyte GPX activity either in ovulatory or anovulatory women was by about 30% higher than in male subjects. Erythrocyte SOD activity in ovulatory women both in follicular and luteal phase of the menstrual cycle (1557 U/g Hb and 1394.6 U/g Hb, respectively was markedly lower than in men (1951.8 and 1937.7 U/g Hb for blood sampling I and II, respectively. In contrast, erythrocyte SOD activity in anovulatory women (1855.5 U/g Hb and 1745.7 U/g Hb in the follicular and luteal phases, respectively was similar to that found in men. The above data indicated that erythrocyte GPX and SOD activities are sensitive to plasma ovarian hormone concentration. In addition, they suggested that due to higher erythrocyte GPX activity females even with anovulatory menstrual cycles are protected better than males against hydrogen peroxide action. However, lower superoxide

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

Science.gov (United States)

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

Science.gov (United States)

Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

2016-05-01

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

International Nuclear Information System (INIS)

Ramadan, L.A.

2003-01-01

In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

Innovative agents in cancer prevention.

Science.gov (United States)

Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

2005-01-01

There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis

Directory of Open Access Journals (Sweden)

Singh Shashank K

2010-12-01

Full Text Available Abstract Background Anticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl naphthalimides (compounds 1a-j were evaluated as antitumor agents. Methods Compounds 1a-j were initially screened in MOLT-4, HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds 1d and 1i were further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound 1i treated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC/PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound 1i were measured at different time intervals. Morphology of the MOLT-4 cells after treatment with 1i was examined under light microscope and transmission electron microscope. 3H-Thymidine and 3H-uridine incorporation in S-180 cells in vitro following treatment with 8 μM concentration of compounds 1d and 1i were studied. Results 6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione (compound 1i, has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC (IC50 value 273 μM. Cell cycle analysis of compound 1i treated MOLT-4 cells demonstrated rise in sub-G1 fraction and concomitant accumulation of cells in S and G2/M phases, indicating up-regulation of apoptosis along with mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in flow cytometric study in MOLT-4 and the action was mediated by activation of both caspase 3 and 6. Light and

Terbinafine-induced lichenoid drug eruption.

Science.gov (United States)

Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

2017-03-01

Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

Effect of green juice and their bioactive compounds on genotoxicity induced by alkylating agents in mice.

Science.gov (United States)

Fagundes, Gabriela Elibio; Damiani, Adriani Paganini; Borges, Gabriela Daminelli; Teixeira, Karina Oliveira; Jesus, Maiellen Martins; Daumann, Francine; Ramlov, Fernanda; Carvalho, Tiago; Leffa, Daniela Dimer; Rohr, Paula; Moraes De Andrade, Vanessa

2017-01-01

Kale juice (Brassica oleracea L. var. acephala D.C.) is a reliable source of dietary carotenoids and typically contains the highest concentrations of lutein (LT) and beta-carotene (BC) among green leafy vegetables. As a result of their antioxidant properties, dietary carotenoids are postulated to decrease the risk of disease occurrence, particularly certain cancers. The present study aimed to (1) examine the genotoxic and antigenotoxic activity of natural and commercially available juices derived from Brassica oleracea and (2) assess influence of LT or BC against DNA damage induced by alkylating agents such as methyl methanesulfonate (MS) or cyclophosphamide (CP) in vivo in mice. Male Swiss mice were divided into groups of 6 animals, which were treated with water, natural, or commercial Brassica oleraceae juices (kale), LT, BC, MMS, or CP. After treatment, DNA damage was determined in peripheral blood lymphocytes using the comet assay. Results demonstrated that none of the Brassica oleraceae juices or carotenoids produced genotoxic effects. In all examined cell types, kale juices or carotenoids inhibited DNA damage induced by MMS or CP administered either pre- or posttreatment by 50 and 20%, respectively. Under our experimental conditions, kale leaf juices alone exerted no marked genotoxic or clastogenic effects. However, a significant decrease in DNA damage induced by MMS or CP was noted. This effect was most pronounced in groups that received juices, rather than carotenoids, suggesting that the synergy among constituents present in the food matrix may be more beneficial than the action of single compounds. Data suggest that the antigenotoxic properties of kale juices may be of therapeutic importance.

Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

International Nuclear Information System (INIS)

Peng, Hui; Wang, Huihui; Xue, Peng; Hou, Yongyong; Dong, Jian; Zhou, Tong; Qu, Weidong; Peng, Shuangqing; Li, Jin; Carmichael, Paul L.; Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

2016-01-01

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As 2 O 3 ), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As 2 O 3 -challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As 2 O 3 -induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As 2 O 3 -induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As 2 O 3 in AML cells. • Sensitization of THP-1 cells to As 2 O 3 toxicity by ethionamide is NRF2-dependent.

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

Science.gov (United States)

Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

Efficacy of ATR inhibitors as single agents in Ewing sarcoma

DEFF Research Database (Denmark)

Nieto-Soler, Maria; Morgado-Palacin, Isabel; Lafarga, Vanesa

2016-01-01

Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source...... efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas....

Bleomycin-induced pneumonitis

NARCIS (Netherlands)

S. Sleijfer (Stefan)

2001-01-01

textabstractThe cytotoxic agent bleomycin is feared for its induction of sometimes fatal pulmonary toxicity, also known as bleomycin-induced pneumonitis (BIP). The central event in the development of BIP is endothelial damage of the lung vasculature due to bleomycin-induced

Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts

International Nuclear Information System (INIS)

Keyse, S.M.; Tyrrell, R.M.

1987-01-01

We have analyzed the pattern of protein synthesis in solar near ultraviolet (334 nm, 365 nm) and near visible (405 nm) irradiated normal human skin fibroblasts. Two hours after irradiation we find that one major stress protein of approximately 32 kDa is induced in irradiated cells. This protein is not induced by ultraviolet radiation at wavelengths shorter than 334 nm and is not inducible by heat shock treatment of these cells. Although sodium arsenite, diamide, and menadione all induced a 32-kDa protein, they also induced the major heat shock proteins. In contrast, the oxidizing agent, hydrogen peroxide, induced the low molecular weight stress protein without causing induction of the major heat shock proteins. A comparison of the 32-kDa proteins induced by sodium arsenite, H 2 O 2 , and solar near ultraviolet radiation using chemical peptide mapping shows that they are closely related. These results imply that the pathways for induction of the heat shock response and the 32-kDa protein are not identical and suggest that, at least in the case of radiation and treatment with H 2 O 2 , the 32-kDa protein might be induced in response to cellular oxidative stress. This conclusion is supported by the observation that depletion of endogenous cellular glutathione prior to solar near ultraviolet irradiation lowers the fluence threshold for induction of the 32-kDa stress protein

Memory effects induce structure in social networks with activity-driven agents

International Nuclear Information System (INIS)

Medus, A D; Dorso, C O

2014-01-01

Activity-driven modelling has recently been proposed as an alternative growth mechanism for time varying networks,displaying power-law degree distribution in time-aggregated representation. This approach assumes memoryless agents developing random connections with total disregard of their previous contacts. Thus, such an assumption leads to time-aggregated random networks that do not reproduce the positive degree-degree correlation and high clustering coefficient widely observed in real social networks. In this paper, we aim to study the incidence of the agents' long-term memory on the emergence of new social ties. To this end, we propose a dynamical network model assuming heterogeneous activity for agents, together with a triadic-closure step as main connectivity mechanism. We show that this simple mechanism provides some of the fundamental topological features expected for real social networks in their time-aggregated picture. We derive analytical results and perform extensive numerical simulations in regimes with and without population growth. Finally, we present an illustrative comparison with two case studies, one comprising face-to-face encounters in a closed gathering, while the other one corresponding to social friendship ties from an online social network. (paper)

The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK-p53-dependent mitochondrial apoptosis in breast cancer cells.

Science.gov (United States)

Zhao, Lin; Li, Yanlin; He, Miao; Song, Zhiguo; Lin, Shu; Yu, Zhaojin; Bai, Xuefeng; Wang, Enhua; Wei, Minjie

2014-07-01

The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to DNA alkylating agents and greatly influences drug response in cancer treatment. However, the molecular mechanisms underlying the FA/BRCA pathway reversed resistance have received limited attention. In the present study, we investigated the effect of Fanconi anemia complementation group F protein (FANCF), a critical factor of the FA/BRCA pathway, on cancer cell apoptosis induced by DNA alkylating agents such as mitomycin c (MMC). We found that FANCF shRNA potentiated MMC-induced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 breast cancer cells. At a mechanistic level, FANCF shRNA downregulated the anti-apoptotic protein Bcl-2 and upregulated the pro-apoptotic protein Bax, accompanied by release of cyt-c and smac into the cytosol in MMC-treated cells. Furthermore, activation of caspase-3 and -9, other than caspase-8, cleavage of poly(ADP ribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated that involvement of the mitochondrial apoptotic pathway in FANCF silencing of MMC-treated breast cancer cells. A decrease in IAP family proteins XIAP and survivin were also observed following FANCF silencing in MMC-treated breast cancer cells. Notably, FANCF shRNA was able to increase p53 levels through activation of the JNK pathway in MMC-treated breast cancer cells. Furthermore, p53 inhibition using pifithrin-α abolished the induction of caspase-3 and PARP by FANCF shRNA and MMC, indicating that MMC-induced apoptosis is substantially enhanced by FANCF shRNA via p53-dependent mechanisms. To our knowledge, we provide new evidence for the potential application of FANCF as a chemosensitizer in breast cancer therapy.

pCramoll and rCramoll as New Preventive Agents against the Oxidative Dysfunction Induced by Hydrogen Peroxide

Directory of Open Access Journals (Sweden)

Luís Cláudio Nascimento da Silva

2015-01-01

Full Text Available Oxidative stress plays an important role in the induction of cell death and is associated with various pathologic disorders; therefore, the search for natural products that attenuate the effects produced by oxidant agents is greatly increased. Here, the protective effects of native lectin from Cratylia mollis seeds (pCramoll and recombinant Cramoll 1 (rCramoll against H2O2-induced oxidative stress in Vero cells were evaluated. Both lectins significantly attenuated the H2O2-induced cytotoxicity in a concentration-dependent way. The maximum protective effects were 96.85±15.59% (rCramoll and 59.48±23.44% (pCramoll. The Live/Dead analysis showed a reduction in the percentage of dead cells from 65.04±3.29% (H2O2 to 39.77±2.93% (pCramoll and 13.90±9.01% (rCramoll. The deleterious effects of H2O2 on cell proliferation were reduced to 10.83% (pCramoll and 24.17% (rCramoll. Lectins treatment attenuated the excessive superoxide production, the collapse of the mitochondrial membrane potential, and the lysosomal and DNA damage in H2O2-treated cells. In conclusion, our results suggest that pCramoll and rCramoll blocked H2O2-induced cytotoxicity through decreasing reactive oxygen species, restoring the mitochondrial potential, preventing the lysosomal damage and DNA fragmentation, and thus promoting cell survival and proliferation.

Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

Science.gov (United States)

Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

2011-10-01

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin

DEFF Research Database (Denmark)

Tan, Hsih-Yin; Loke, Weng Keong; Nguyen, Nam-Trung

2014-01-01

This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based on rapid electrochemical detection. The chemical warfare agent Sarin (C4H10FO2P, O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that induces rapid respiratory depression, seizures and death...

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

Science.gov (United States)

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

International Nuclear Information System (INIS)

Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

2012-01-01

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA A receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death. �

Cynodon dactylon extract as a preventive and curative agent in experimentally induced nephrolithiasis.

Science.gov (United States)

Atmani, F; Sadki, C; Aziz, M; Mimouni, M; Hacht, B

2009-04-01

Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney stones. However, no scientific study was undertaken so far to demonstrate the beneficial effect of the plant. Thus, the aim of the current study is to evaluate the effect of Cynodon aqueous extract as a preventive and curative agent in experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys. In preventive protocol, Cynodon decoction was administered in the same day with EG to evaluate the ability of the extract to prevent crystal deposition. However, in curative protocol, rats were first rendered nephrolithiasic and then the extract was administered to assess the ability of the plant to eliminate the pre-existing crystal deposition. In both protocols, urinary biochemical and other variables were measured during the course of the study. Crystalluria and renal histology were examined as well. The results showed that, in both protocols, all measured variables were similar for both the rat groups. Nevertheless, urinary biochemical analysis was apparently unaffected by the extract except oxalate in preventive protocol, and calcium, sodium, and potassium in curative protocol which were significantly highly excreted in treated rats compared to untreated animals. Crystalluria was characterized mostly by the presence of large quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats. However, crystalluria was mainly dominated by the presence of CaOx dihydrate particles with reduced size. The most apparent beneficial effect of Cynodon extract was seen in kidney tissues where reduced levels of CaOx deposition have been noticed especially in medullary and papillary sections from treated rats. We concluded that C. dactylon extract has beneficial effect in preventing and eliminating CaOx deposition into kidneys. Such findings provide a scientific explanation for its use in the

Chemical warfare agents. Classes and targets.

Science.gov (United States)

Schwenk, Michael

2018-09-01

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.

Science.gov (United States)

Bayir, Yasin; Halici, Zekai; Keles, Mevlut Sait; Colak, Suat; Cakir, Ahmet; Kaya, Yusuf; Akçay, Fatih

2011-11-18

Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Antibacterial Cell Division Inhibitor PC190723 Is an FtsZ Polymer-stabilizing Agent That Induces Filament Assembly and Condensation*

Science.gov (United States)

Andreu, José M.; Schaffner-Barbero, Claudia; Huecas, Sonia; Alonso, Dulce; Lopez-Rodriguez, María L.; Ruiz-Avila, Laura B.; Núñez-Ramírez, Rafael; Llorca, Oscar; Martín-Galiano, Antonio J.

2010-01-01

Cell division protein FtsZ can form single-stranded filaments with a cooperative behavior by self-switching assembly. Subsequent condensation and bending of FtsZ filaments are important for the formation and constriction of the cytokinetic ring. PC190723 is an effective bactericidal cell division inhibitor that targets FtsZ in the pathogen Staphylococcus aureus and Bacillus subtilis and does not affect Escherichia coli cells, which apparently binds to a zone equivalent to the binding site of the antitumor drug taxol in tubulin (Haydon, D. J., Stokes, N. R., Ure, R., Galbraith, G., Bennett, J. M., Brown, D. R., Baker, P. J., Barynin, V. V., Rice, D. W., Sedelnikova, S. E., Heal, J. R., Sheridan, J. M., Aiwale, S. T., Chauhan, P. K., Srivastava, A., Taneja, A., Collins, I., Errington, J., and Czaplewski, L. G. (2008) Science 312, 1673–1675). We have found that the benzamide derivative PC190723 is an FtsZ polymer-stabilizing agent. PC190723 induced nucleated assembly of Bs-FtsZ into single-stranded coiled protofilaments and polymorphic condensates, including bundles, coils, and toroids, whose formation could be modulated with different solution conditions. Under conditions for reversible assembly of Bs-FtsZ, PC190723 binding reduced the GTPase activity and induced the formation of straight bundles and ribbons, which was also observed with Sa-FtsZ but not with nonsusceptible Ec-FtsZ. The fragment 2,6-difluoro-3-methoxybenzamide also induced Bs-FtsZ bundling. We propose that polymer stabilization by PC190723 suppresses in vivo FtsZ polymer dynamics and bacterial division. The biochemical action of PC190723 on FtsZ parallels that of the microtubule-stabilizing agent taxol on the eukaryotic structural homologue tubulin. Both taxol and PC190723 stabilize polymers against disassembly by preferential binding to each assembled protein. It is yet to be investigated whether both ligands target structurally related assembly switches. PMID:20212044

Oral Contraceptives and Bone Health in Female Runners

National Research Council Canada - National Science Library

Kelsey, Jennifer L

2007-01-01

.... Previous cross-sectional research has shown that women with exercise-induced menstrual irregularities have a significantly higher frequency of stress fractures and low bone mass than normally menstruating controls...

Trio of terror (pregnancy, menstruation, and breastfeeding): an existential function of literal self-objectification among women.

Science.gov (United States)

Morris, Kasey Lynn; Goldenberg, Jamie L; Heflick, Nathan A

2014-07-01

Research and theorizing suggest that objectification entails perceiving a person not as a human being but, quite literally, as an object. However, the motive to regard the self as an object is not well understood. The current research tested the hypothesis that literal self-objectification can serve a terror management function. From this perspective, the female body poses a unique existential threat on account of its role in reproduction, and regarding the self as an object is posited to shield women from this threat because objects, in contrast to humans, are not mortal. Across 5 studies, 3 operationalizations of literal self-objectification were employed (a denial of essentially human traits to the self, overlap in the explicit assignment of traits to the self and objects, and implicit associations between self and objects using an implicit association test) in response to 3 aspects of women's bodies involved in reproduction (pregnancy, menstruation, and breastfeeding). In each study, priming mortality led women (but not men, included in Studies 1, 3, 4, and 5) to literally self-objectify in conditions where women's reproductive features were salient. In addition, literal self-objectification was found to mediate subsequent responsiveness to death-related stimuli (Study 4). Together, these findings are the first to demonstrate a direct link between mortality salience, women's role in reproduction, and their self-objectification, supporting an existential function of self-objectification in women.

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

Science.gov (United States)

Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

International Nuclear Information System (INIS)

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

2012-01-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Energy Technology Data Exchange (ETDEWEB)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

2012-10-01

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

SIMULATING AN EVOLUTIONARY MULTI-AGENT BASED MODEL OF THE STOCK MARKET

Directory of Open Access Journals (Sweden)

Diana MARICA

2015-08-01

Full Text Available The paper focuses on artificial stock market simulations using a multi-agent model incorporating 2,000 heterogeneous agents interacting on the artificial market. The agents interaction is due to trading activity on the market through a call auction trading mechanism. The multi-agent model uses evolutionary techniques such as genetic programming in order to generate an adaptive and evolving population of agents. Each artificial agent is endowed with wealth and a genetic programming induced trading strategy. The trading strategy evolves and adapts to the new market conditions through a process called breeding, which implies that at each simulation step, new agents with better trading strategies are generated by the model, from recombining the best performing trading strategies and replacing the agents which have the worst performing trading strategies. The simulation model was build with the help of the simulation software Altreva Adaptive Modeler which offers a suitable platform for financial market simulations of evolutionary agent based models, the S&P500 composite index being used as a benchmark for the simulation results.

DNA damage-inducible transcripts in mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Alamo, I. Jr.; Hollander, M.C.

1988-01-01

Hybridization subtraction at low ratios of RNA to cDNA was used to enrich for the cDNA of transcripts increased in Chinese hamster cells after UV irradiation. Forty-nine different cDNA clones were isolated. Most coded for nonabundant transcripts rapidly induced 2- to 10-fold after UV irradiation. Only 2 of the 20 cDNA clones sequenced matched known sequences (metallothionein I and II). The predicted amino acid sequence of one cDNA had two localized areas of homology with the rat helix-destabilizing protein. These areas of homology were at the two DNA-binding sites of this nucleic acid single-strand-binding protein. The induced transcripts were separated into two general classes. Class I transcripts were induced by UV radiation and not by the alkylating agent methyl methanesulfonate. Class II transcripts were induced by UV radiation and by methyl methanesulfonate. Many class II transcripts were induced also by H2O2 and various alkylating agents but not by heat shock, phorbol 12-tetradecanoate 13-acetate, or DNA-damaging agents which do not produce high levels of base damage. Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury

Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.

Science.gov (United States)

Allen, Joshua E; Krigsfeld, Gabriel; Patel, Luv; Mayes, Patrick A; Dicker, David T; Wu, Gen Sheng; El-Deiry, Wafik S

2015-05-01

We previously reported the identification of ONC201/TIC10, a novel small molecule inducer of the human TRAIL gene that improves efficacy-limiting properties of recombinant TRAIL and is in clinical trials in advanced cancers based on its promising safety and antitumor efficacy in several preclinical models. We performed a high throughput luciferase reporter screen using the NCI Diversity Set II to identify TRAIL-inducing compounds. Small molecule-mediated induction of TRAIL reporter activity was relatively modest and the majority of the hit compounds induced low levels of TRAIL upregulation. Among the candidate TRAIL-inducing compounds, TIC9 and ONC201/TIC10 induced sustained TRAIL upregulation and apoptosis in tumor cells in vitro and in vivo. However, ONC201/TIC10 potentiated tumor cell death while sparing normal cells, unlike TIC9, and lacked genotoxicity in normal fibroblasts. Investigating the effects of TRAIL-inducing compounds on cell signaling pathways revealed that TIC9 and ONC201/TIC10, which are the most potent inducers of cell death, exclusively activate Foxo3a through inactivation of Akt/ERK to upregulate TRAIL and its pro-apoptotic death receptor DR5. These studies reveal the selective activity of ONC201/TIC10 that led to its selection as a lead compound for this novel class of antitumor agents and suggest that ONC201/TIC10 is a unique inducer of the TRAIL pathway through its concomitant regulation of the TRAIL ligand and its death receptor DR5.

Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10

OpenAIRE

Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; van den Heuvel, AP; Lim, Bora; Dicker, David T.; Fritz, Jennifer L.; Beck, Adam; El-Deiry, Wafik S.

2015-01-01

ONC201/TIC10 is a small molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway inducer KSR1. Unexpectedly, KSR1 sile...

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

Science.gov (United States)

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis

DEFF Research Database (Denmark)

Bronckers, Inge M G J; Seyger, Marieke M B; West, Dennis P

2017-01-01

Importance: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. Objective: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. Design, Setting,...... per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis....

Balancing repair and tolerance of DNA damage caused by alkylating agents.

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

Identification of chemical warfare agent with radiological measurements

International Nuclear Information System (INIS)

Liu Boxue; Li Yun; Ai Xianyun

2000-01-01

There are three non-destructive radiological methods for identification of warfare agents and TNT. Their principles and problems related were discussed. Portable isotopic neutron spectroscopy is based on the assay of key elemental composition (such as Cl, P, H, As, S, N) in chemical agents by neutron induced prompt gamma ray analysis. Hydrogen concentration measurement by means of using thermal neutron can be employed to identify chemical warfare agents and TNT that contains different hydrogen fraction. The calibration curves of thermal neutron count rate against hydrogen concentration were measured. X ray imagination system can be used to determine the internal structure of chemical bombs, there by to identify them. The radiological methods are very useful for identification of old chemical weapons abandoned by Japan Army during World War 2

Injectable agents affecting subcutaneous fats.

Science.gov (United States)

Chen, David Lk; Cohen, Joel L; Green, Jeremy B

2015-09-01

Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1

International Nuclear Information System (INIS)

Moehler, Markus; Sieben, Maike; Roth, Susanne; Springsguth, Franziska; Leuchs, Barbara; Zeidler, Maja; Dinsart, Christiane; Rommelaere, Jean; Galle, Peter R

2011-01-01

Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV. Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC). H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone. In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine

AFRREV, 9(1), S/NO 36, JANUARY, 2015

African Journals Online (AJOL)

EMILIA

values are fast shifting with changes in Ikwerre religious beliefs and practices. Records such ... to Ali deity. However, the story of the impact of Christianity and other agents .... eat food cooked by a woman in menstruation, or to sit or have sexual intercourse on .... It was the fear that one might die bad death either with swollen ...

Environmental exposure and altered menstrual function

Energy Technology Data Exchange (ETDEWEB)

Keye, W.R. Jr.

1984-01-01

The impact of environmental agents and occupational factors on hypothalamic and pituitary function and menstruation are poorly understood. To date, most research related to environment, occupation, and reproduction has focused on pregnancy outcome, not menstrual function. It is imperative, however, that menstrual function be considered as an outcome variable in the study of reproduction and occupation.

Radioprotective Agents

Directory of Open Access Journals (Sweden)

Ilker Kelle

2008-01-01

Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

Mechanisms of chemoresistance to alkylating agents in malignant glioma.

Science.gov (United States)

Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

2008-05-15

Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Peng, Hui [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Wang, Huihui [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Xue, Peng [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Hou, Yongyong [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Dong, Jian [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan (China); Zhou, Tong [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Peng, Shuangqing [Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Li, Jin; Carmichael, Paul L. [Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Pi, Jingbo, E-mail: jpi@mail.cmu.edu.cn [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States)

2016-02-01

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As{sub 2}O{sub 3}), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As{sub 2}O{sub 3}-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As{sub 2}O{sub 3}-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As{sub 2}O{sub 3}-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As{sub 2}O{sub 3} in AML cells. • Sensitization of THP-1 cells to As{sub 2}O{sub 3} toxicity by ethionamide is NRF2-dependent.

Comparison of alkylating agent and radiation carcinogenesis: some aspects of the possible involvement of effects on DNA

International Nuclear Information System (INIS)

Lawley, P.D.

1976-01-01

A series of alkylating agents was classified in terms of increasing relative ability to react at O-atom sites in DNA, MMS 6 -alkylguanines are directly miscoding bases. This series of agents was also used in a study of comparative carcinogenicity with respect to induction of thymic lymphoma in mice, a system in which x-irradiation yields tumors. A positive correlation between ability of agents to alkylate O-6 of guanine in DNA of thymus and carcinogenic potency was found. Although MMS was not active in this system, it was noted that it can induce tumors in other systems. The relationship between repair of alkylation and radiation induced damage in DNA was briefly discussed. The methylating agents induce single-strand breaks in DNA, and the principal repair system appears to fall into the category of short repair as denoted by Regan and Setlow (1974). These single-strand breaks may result from spontaneous hydrolytic depurinations of 3- and 7-methylpurines, or from enzymatic depurinations, e.g., of 3-alkyladenine and O 6 -alkylguanine. Aralkylating agents, which are also carcinogens, can evoke an alternative repair response of the uvr type

Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

Science.gov (United States)

Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

2017-11-05

Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Attitudes toward menstruation, menstrual-related symptoms, and premenstrual syndrome among adolescent girls: a rural school-based survey.

Science.gov (United States)

Wong, Li Ping

2011-06-21

Folk culture surrounding menstrual-related matters has considerable implications for symptom expression and treatment-seeking behavior. A cross-sectional survey of 1,295 rural adolescent girls aged 13 to 19 years was conducted between February 4 and April 16, 2009 to examine these associations. With a higher score indicating a more positive attitude toward menstruation, the mean attitude score was 3.84 (SD ± 1.62) out of a maximum of six. No significant association was observed between the severity of menstrual symptoms and attitudes. Most (63.1%) of the participants identified themselves as having premenstrual symptoms, and 61.1% viewed premenstrual symptoms as a normal part of menstrual cycle. Participants with a higher severity of symptoms in the premenstrual (OR 1.05, 95% CI 1.01-1.10) and menstrual phase (OR 1.04, 95% CI 1.01-1.07), were more likely to consult a physician for premenstrual symptoms, and having a divorced/separated parents was associated with a reduced odds of consulting a physician compared to those having parents that were married (OR 0.19, 95% CI 0.05-0.83). The findings imply the need for education to help adolescent girls manage menstrual symptoms and increase awareness of the benefit of treating them. Given that menstrual-related information was widely available from mothers, family, and social culture are potentially important in shaping good menstrual attitudes.

Different G2/M accumulation in M059J and M059K cells after exposure to DNA double-strand break-inducing agents

International Nuclear Information System (INIS)

Holgersson, Asa; Heiden, Thomas; Castro, Juan; Edgren, Margareta R.; Lewensohn, Rolf; Meijer, Annelie E.

2005-01-01

Purpose: To investigate and compare the cell cycle progression in relation to cell death in the human glioma cell lines, M059J and M059K, after exposure to DNA double-strand break-inducing agents. Methods and materials: The M059J and M059K cells, deficient and proficient in the catalytic subunit of the DNA-dependent protein kinase, respectively, were exposed to 1 and 4 Gy of photons or accelerated nitrogen ions. In addition, M059J and M059K cells were treated with 10 and 40 μg/mL of bleomycin for 30 min, respectively. Cell cycle progression, monitored by DNA flow cytometry, was measured up to 72 h after treatment. Results: M059J, but not M059K, cells displayed G 2 /M accumulation after low linear energy transfer irradiation. High linear energy transfer radiation exposure however, resulted in a substantial increase of M059K cells in the G 2 /M phase detected at 48 h. At 72 h, the number of cells in the G 2 /M phase was equivalent to its control. M059J cells accumulated mainly in S phase after high linear energy transfer irradiation. In contrast to M059K, M059J cells were still blocked at 72 h. Bleomycin induced G 2 /M accumulation for both M059J and M059K cells detected 24 h after treatment. At 48 h, the percentage of bleomycin-treated M059J cells in G 2 /M phase remained high, and the number of M059K cells had decreased to control levels. Neither cell line showed cell cycle arrest (≤10 h) after exposure to these agents. Conclusion: Distinct cell cycle block and release is dependent on the complexity of the induced DNA damage and the presence of the DNA-dependent protein kinase catalytic subunit

LABORATORY EXAMINATION IN NERVE AGENT INTOXICATION

Directory of Open Access Journals (Sweden)

Jiří Bajgar

2013-01-01

Full Text Available Diagnosis of nerve agent intoxication is based on anamnestic data, clinical signs and laboratory examination. For acute poisoning, cholinesterase activity in the blood (erythrocyte AChE, plasma/serum BuChE is sensitive, simple and most frequent laboratory examination performed in biochemical laboratories. Specialized examinations to precise treatment (reactivation test or to make retrospective diagnosis (fluoride induced reactivation etc. can be conducted. Other sophisticated methods are available, too.

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

Science.gov (United States)

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

1972-01-01

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

Mutagenic effects of alkylating agents on prophage lambda

Energy Technology Data Exchange (ETDEWEB)

Bresler, S.; Kalinin, V.L.; Kuznetsova, L.V.

1984-06-01

An evaluation was made of the relative contribution of repair and reparative mechanisms to the mutagenic potency of several alkylating agents on thermoinducible prophage lambdacI857 ind/sup -/ in several stains of E. coli. Following treatment of lysogenic E. coli with the mutagens and heat induction, 0.02 N-nitroso-N-methylurea (NMU) induced c mutations with a high frequency (ca. 10%) in both wild type E. coli and cells with repair mutations (recA13, lexA102, uvrA6, umuC36, xthA9, recF143, polA1, uvrD3, uvrD502). It appears that NUM-induced mutations are stabilized as replicative errors due to mismatched, altered bases. Delay in induction following exposure to NMU improves prophage survival and diminishes c mutant formation, regardless of the E. coli genotype. Evidently, carbamoylation is not involved in NMU mutagenicity since 0.02 M KNCO is nonmutagenic and is virtually without effect on prophage viability. Replicative mechanisms are also involved in N-methyl-N'-nitro-N-nitrosoguanidine (15%) and ethyl methanesulfonate (2%) induced mutations, since the maximum yield of mutants was independent of recA/sup +/ genotype. However, the mutagenicity of methyl methanesulfonate was abolished by the recA mutation, indicating that the mutagenicity of this agent is repair-dependent. Mitomycin C (0.1%) and acridine mustard (0.3%) induce c mutations regardless of recA/sup +/ and, therefore, appear to do so by intercalation. 26 references, 6 figures.

Oxaliplatin-induced neuropathy in colorectal cancer

DEFF Research Database (Denmark)

Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa

2014-01-01

Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...

Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

Energy Technology Data Exchange (ETDEWEB)

Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

2014-10-15

Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

Prophage induction in Haemophilus influenzae and its relationship to mutation by chemical and physical agents

International Nuclear Information System (INIS)

Balganesh, M.; Setlow, J.K.

1984-01-01

It is known that UV, X-rays, MMC and MMS are not mutagenic for H. influenzae, whereas HZ, EMS and MNNG are potent mutagens for this bacterium. All of these agents, however, are known to be both mutagenic and able to induce prophage in E. coli. We report here that all the agents except HZ induce prophage in H. influenzae, and EMS even induces in the recombination-defective recl mutant, which is non-inducible by UV, MMC, MNNG and MMS. MMS did not cause single-strand breaks or gaps in DNA synthesized after treatment of H. influenzae, but EMS and MNNG produced them. EMS caused more breaks in DNA synthesized before treatment than in that synthesized after treatment. On the other hand we did observe such breaks or gaps induced in E. coli in DNA synthesized posttreatment by EMS as well as by MMS and MNNG, at comparable survival levels. (orig.)

Prophage induction in Haemophilus influenzae and its relationship to mutation by chemical and physical agents

Energy Technology Data Exchange (ETDEWEB)

Balganesh, M.; Setlow, J.K. (Brookhaven National Lab., Upton, NY (USA))

1984-01-01

It is known that UV, X-rays, MMC and MMS are not mutagenic for H. influenzae, whereas HZ, EMS and MNNG are potent mutagens for this bacterium. All of these agents, however, are known to be both mutagenic and able to induce prophage in E. coli. We report here that all the agents except HZ induce prophage in H. influenzae, and EMS even induces in the recombination-defective recl mutant, which is non-inducible by UV, MMC, MNNG and MMS. MMS did not cause single-strand breaks or gaps in DNA synthesized after treatment of H. influenzae, but EMS and MNNG produced them. EMS caused more breaks in DNA synthesized before treatment than in that synthesized after treatment. On the other hand we did observe such breaks or gaps induced in E. coli in DNA synthesized posttreatment by EMS as well as by MMS and MNNG, at comparable survival levels.

Detection of DNA damage induced in vivo by a cross-linking agent with a circular channel crucible oscillating viscometer.

Science.gov (United States)

Balbi, C; Abelmoschi, M L; Roner, R; Giaretti, W; Parodi, S; Santi, L

1985-11-01

DNA damage induced in vivo by the cross-linking agent mitomycin C (MMC) was investigated with a new oscillating crucible viscometer. Viscosity was measured by lysing rat liver nuclei in an alkaline lysing solution (pH 12.5; 25 degrees C). In control samples the viscosity increased very slowly with time, reaching a plateau only after 10-12 h. The process was accelerated and the maximum viscosity was decreased by alkaline single-stranded breaks arising from methylation and subsequent depurination of DNA in vitro with dimethylsulphate (DMS). MMC, when given alone, had no evident effect on the time needed for reaching plateau viscosity but it induced a small increase in maximum viscosity. When MMC was given in association with DMS, the time of disentanglement remained unchanged (accelerated) but maximum viscosity was increased in a dose dependent way. We conclude that these data clearly confirm that the slow steady increase of the viscosity of control DNA with time reflects mainly the process of unwinding of the two strands. The speed of this process seems to depend only from the number of unwinding points in DNA (breaks).

Managing Phytophthora crown and root rot on tomato by pre-plant treatments with biocontrol agents, resistance inducers, organic and mineral fertilizers under nursery conditions

Directory of Open Access Journals (Sweden)

Giovanna GILARDI

2014-09-01

Full Text Available Five trials were carried out under greenhouse conditions to test the efficacy of spray programmes based on biocontrol agents, phosphite-based fertilizers and a chemical inducer of resistance (acibenzolar-S-methyl, phosethyl-Al to control crown and root rot of tomato incited by Phytophthora nicotianae. The best disease control, under high disease pressure resulting from artificial inoculation, was obtained with three pre-plant leaf sprays at 7 d intervals with acibenzolar-S-methyl and with two mineral phosphite-based fertilizers. The disease reduction achieved was similar to that obtained with a single application of azoxystrobin and metalaxyl-M. Phosetyl-Al and the biocontrol agents Glomus spp. + Bacillus megaterium + Trichoderma, B. subtilis QST713, B. velezensis IT45 and the mixture T. asperellum ICC012 + T. gamsii ICC080 provided a partial disease control. Brassica carinata pellets did not control the disease.

Can human-like Bots control collective mood: agent-based simulations of online chats

Science.gov (United States)

Tadić, Bosiljka; Šuvakov, Milovan

2013-10-01

Using an agent-based modeling approach, in this paper, we study self-organized dynamics of interacting agents in the presence of chat Bots. Different Bots with tunable ‘human-like’ attributes, which exchange emotional messages with agents, are considered, and the collective emotional behavior of agents is quantitatively analyzed. In particular, using detrended fractal analysis we determine persistent fluctuations and temporal correlations in time series of agent activity and statistics of avalanches carrying emotional messages of agents when Bots favoring positive/negative affects are active. We determine the impact of Bots and identify parameters that can modulate that impact. Our analysis suggests that, by these measures, the emotional Bots induce collective emotion among interacting agents by suitably altering the fractal characteristics of the underlying stochastic process. Positive emotion Bots are slightly more effective than negative emotion Bots. Moreover, Bots which periodically alternate between positive and negative emotion can enhance fluctuations in the system, leading to avalanches of agent messages that are reminiscent of self-organized critical states.

REM sleep pathways and anticholinesterase intoxication: A mechanism for nerve agent-induced, central respiratory failure.

NARCIS (Netherlands)

Kok, A.

1993-01-01

The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosphate anticholinesterases such as the insecticide parathion, remains unclear, although evidence from nerve agent research suggests that death occurs by an

Interactions of radiation with novel chemotherapeutic agents: Taxanes and nucleoside analogs

International Nuclear Information System (INIS)

Milas, Luka

1997-01-01

The combination of chemotherapeutic agents and radiotherapy is an appealing approach to improving the results of cancer treatment. By their independent action or interactive action chemotherapeutic drugs reduce cell burden in tumors undergoing radiotherapy, thereby increasing the chances of tumor control. In addition, the drugs may spatially cooperate with radiotherapy through their systemic action on metastatic disease. Recently, a number of new chemotherapeutic agents have been introduced for cancer treatment, which in addition have high potential to increase therapeutic ratio of radiotherapy. These agents include taxanes (paclitaxel and docetaxel) and the nucleoside analogs fludarabine and gemcitabine. Paclitaxel is a natural product isolated from the bark of Taxus brevifolia and taxotere is a semisynthetic analogue of paclitaxel prepared from needle extracts of Taxus baccata. By binding to cellular tubulin structures, taxanes interfere with tubulin polymerization and promote microtubule assembly, resulting in accumulation of cells in the radiosensitive G2 and M phases of the cell cycle. In vivo studies have demonstrated two major mechanisms of tumor radioenhancement by taxanes: mitotic arrest and tumor reoxygenation. Fludarabine and gemcitabine inhibit DNA synthesis and the repair of radiation-induced chromosome breaks. The mechanism of their radioenhancing activity include inhibition of repair of radiation induced damage, apoptosis induction and cell cycle synchronization. Because both classes of these agents affect radioresponse of normal dose-limiting tissues much less than that of tumors, they can greatly increase therapeutic ratio of radiotherapy. The objective of this course is to overview the rationale for using these drugs as radioenhancing agents, the experimental findings in preclinical studies, the mechanisms of their interaction, and the clinical application of these agents

Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

International Nuclear Information System (INIS)

Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

1996-01-01

The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

Science.gov (United States)

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Exercise-Induced Rhabdomyolysis and Stress-Induced Malignant Hyperthermia Events, Association with Malignant Hyperthermia Susceptibility, and RYR1 Gene Sequence Variations

Directory of Open Access Journals (Sweden)

Antonella Carsana

2013-01-01

Full Text Available Exertional rhabdomyolysis (ER and stress-induced malignant hyperthermia (MH events are syndromes that primarily afflict military recruits in basic training and athletes. Events similar to those occurring in ER and in stress-induced MH events are triggered after exposure to anesthetic agents in MH-susceptible (MHS patients. MH is an autosomal dominant hypermetabolic condition that occurs in genetically predisposed subjects during general anesthesia, induced by commonly used volatile anesthetics and/or the neuromuscular blocking agent succinylcholine. Triggering agents cause an altered intracellular calcium regulation. Mutations in RYR1 gene have been found in about 70% of MH families. The RYR1 gene encodes the skeletal muscle calcium release channel of the sarcoplasmic reticulum, commonly known as ryanodine receptor type 1 (RYR1. The present work reviews the documented cases of ER or of stress-induced MH events in which RYR1 sequence variations, associated or possibly associated to MHS status, have been identified.

Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

Directory of Open Access Journals (Sweden)

Mei-Fen Chen

2014-01-01

Full Text Available It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R may reduce the blood pressure in spontaneously hypertensive rats (SHRs. Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s. Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

Organizational coordination and costly communication with boundedly rational agents

DEFF Research Database (Denmark)

Dietrichson, Jens; Jochem, Torsten

How does costly communication affect organizational coordination? This paper develops a model of costly communication based on the weakest-link game and boundedly rational agents. Solving for the stochastically stable states, we find that communication increases the possibilities for efficient...... coordination compared to a setting where agents cannot communicate. But as agents face a trade-off between lowering the strategic uncertainty for the group and the costs of communication, the least efficient state is still the unique stochastically stable one for many parameter values. Simulations show...... that this is not just a long run phenomena, the stochastically stable state is the most frequent outcome also in the short run. Making communication mandatory induces efficient coordination, whereas letting a team leader handle communication increases efficiency when the leader expects others to follow and has enough...

Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. (Reannouncement with new availability information)

Energy Technology Data Exchange (ETDEWEB)

Capacio, B.R.; Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Gales, V.

1992-12-31

The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

Science.gov (United States)

Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

Agent Programming Languages and Logics in Agent-Based Simulation

DEFF Research Database (Denmark)

Larsen, John

2018-01-01

and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

Science.gov (United States)

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

Potent heme-degrading action of antimony and antimony-containing parasiticidal agents.

Science.gov (United States)

Drummond, G S; Kappas, A

1981-02-01

The ability of antimony and antimony-containing parasiticidal agents to enhance the rate of heme degradation in liver and kidney was investigated. Trivalent antimony was shown to be an extremely potent inducer of heme oxygenase, the initial and rate-limiting enzyme in heme degradation, in both organs, whereas the pentavalent form was a weak inducer of this enzyme. The ability of antimony to induce heme oxygenase was dose-dependent, independent of the salt used, and not a result of a direct activation of the enzyme in vitro. Concomitant with heme oxygenase induction by antimony, microsomal heme and cytochrome P-450 contents decreased, the cyto-chrome P-450-dependent mixed function oxidase system was impaired, and delta-ami-nolevulinate synthase (ALAS), the rate-limiting enzyme of heme synthesis, underwent the sequential changes-initial inhibition followed by rebound induction-usually associated with the administration of transition elements such as cobalt. Antimony induction of heme oxygenase however, unlike the enzyme induction elicited by cobalt, was not prevented either by cysteine administered orally or as a cysteine metal complex, or by simultaneous zinc administration. Desferoxamine also did not block heme oxygenase induction by antimony, but this chelator did prevent the rebound increase in ALAS activity associated with antimony or cobalt treatment. Antimony-containing parasiticidal drugs were also potent inducers of heme oxygenase in liver and kidney. The heme degradative action of these drugs may be related in part to the jaundice commonly associated with the prolonged therapeutic use of these agents. The heme-oxygenase-inducing action of antimony-containing parasiticidal drugs is a newly defined biological property of these compounds. The relation between the parasiticidal and the heme-oxygenase-inducing actions of such drugs is unknown. However, certain parasites contain hemoproteins or require heme compounds during their life cycle. It may therefore be

Agents unleashed a public domain look at agent technology

CERN Document Server

Wayner, Peter

1995-01-01

Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

OpenAIRE

RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

2014-01-01

Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic ef...

Terminalia catappa , an anticlastogenic agent against MMS induced ...

African Journals Online (AJOL)

Subjects: Anticarcinogenic potential of methanolic extract of T. catappa has been tested against the carcinogenicity induced by methyl methanesulfonate in the in vitro and in vivo models. Methods: The parameters for evaluation included chromosomal aberrations (CA), sister chromatid exchanges (SCEs) and replication ...

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

Science.gov (United States)

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Mobile Agent Data Integrity Using Multi-Agent Architecture

National Research Council Canada - National Science Library

McDonald, Jeffrey

2004-01-01

.... Security issues for mobile agents continue to produce research interest, particularly in developing mechanisms that guarantee protection of agent data and agent computations in the presence of malicious hosts...

Lesão aguda esôfago - gástrica causada por agente químico Chemically induced esophagogastric acute injury

Directory of Open Access Journals (Sweden)

P. R. Corsi

2000-06-01

Full Text Available O tratamento da ingestão de agentes químicos corrosivos continua controverso. A incidência desses episódios tem aumentado nas últimas décadas por várias razões. OBJETIVO: Analisar a ocorrência, as complicações e os resultados do tratamento da lesão esôfago - gástrica causada por agentes químicos. MÉTODOS: Foram estudados retrospectivamente 21 pacientes adultos com lesão esôfago-gástrica, causada por ingestão de substância química, admitidos até 23 dias após o episódio, no Serviço de Emergência da Santa Casa de Misericórdia de São Paulo num período de 12 anos. A média de idade foi 32,1 anos e 11 doentes pertenciam ao sexo feminino, as quais mais freqüentemente tinham intenções suicidas. A soda cáustica foi o produto mais ingerido (76,2%, ingestão de ácido muriático ocorreu em três casos (14,3%, amoníaco e ácido sulfúrico em um caso (4,8% cada. RESULTADOS: As lesões faríngeas e laríngeas estiveram freqüentemente associadas às lesões de esôfago, presentes em 18 casos (85,7%. As lesões esofágicas, gástricas e duodenais foram avaliadas e classificadas por endoscopia. Lesões graves esofágicas ou gástricas estiveram presentes em cinco casos cada. CONCLUSÃO: O tratamento e os resultados foram variados, mas sugeriram que a sondagem esofágica foi prejudicial. A mortalidade global foi 28,6%, mais elevada na lesão esofágica grau 3.Treatment of chemical agent ingestion remain controversial. The incidence of these episodes has increased over the several last decades due to a variety reasons. PURPOSE: To analise the occurance, complications and results of the treatment of chemically induced esophagogastric injury. METHODS: Twenty-one adult patients with chemically induced esophagogastric injury were retrospectively studied. The patients were admitted up to 23 days after ingestion of a chemical agent to the Emergency Department of Santa Casa of Sao Paulo University Hospital from August, in a 12-year

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

Energy Technology Data Exchange (ETDEWEB)

Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu [Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, 10595 (United States); Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Velíšková, Jana [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Stanton, Patric K., E-mail: patric_stanton@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Velíšek, Libor [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Department of Pediatrics, New York Medical College, Valhalla, NY 10595 (United States)

2012-11-15

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death

Drug-induced apnea.

Science.gov (United States)

Boutroy, M J

1994-01-01

Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

Relationship between motion sickness, migraine and menstruation in crew members of a "round the world" yacht race.

Science.gov (United States)

Grunfeld, E; Gresty, M A

1998-11-15

The similarities between the symptoms reported by patients with migraine and those experienced by severely motion sick individuals raises the question of whether the two conditions involve common mechanisms. In women, attacks of migraine may follow the menstrual cycle, and anecdote suggests this may also be true of motion sickness. The aim of this study was to determine whether there was a cyclical pattern in the occurrence of migraine/headache and motion sickness among crew members of a "round the world" yacht race. The participants were asked to complete pre- and postrace questionnaires that related to their susceptibility to motion sickness and headache/migraine; additionally, the female subjects were asked for details about their menstrual cycle. During the race the subjects completed a logbook to record the occurrence of motion sickness (using a four-point scale), migraine/headache (including the type of headache), menstruation, medication consumption and duties aboard the yacht. Female sailors were found to be more prone to motion sickness than the males. Motion sickness was also found to be linked to time at sea, and subjects who suffered migraine during the race were also more susceptible to motion sickness. A distinct pattern was found in the occurrence of motion sickness and headache that related to the menstrual cycle, although motion sickness and headache did not generally occur together in most of the subjects. A cyclical pattern was not obvious for the male subjects.

Industrial antifoam agents impair ethanol fermentation and induce stress responses in yeast cells.

Science.gov (United States)

Nielsen, Jens Christian; Senne de Oliveira Lino, Felipe; Rasmussen, Thomas Gundelund; Thykær, Jette; Workman, Christopher T; Basso, Thiago Olitta

2017-11-01

The Brazilian sugarcane industry constitutes one of the biggest and most efficient ethanol production processes in the world. Brazilian ethanol production utilizes a unique process, which includes cell recycling, acid wash, and non-aseptic conditions. Process characteristics, such as extensive CO 2 generation, poor quality of raw materials, and frequent contaminations, all lead to excessive foam formation during fermentations, which is treated with antifoam agents (AFA). In this study, we have investigated the impact of industrial AFA treatments on the physiology and transcriptome of the industrial ethanol strain Saccharomyces cerevisiae CAT-1. The investigated AFA included industrially used AFA acquired from Brazilian ethanol plants and commercially available AFA commonly used in the fermentation literature. In batch fermentations, it was shown that industrial AFA compromised growth rates and glucose uptake rates, while commercial AFA had no effect in concentrations relevant for defoaming purposes. Industrial AFA were further tested in laboratory scale simulations of the Brazilian ethanol production process and proved to decrease cell viability compared to the control, and the effects were intensified with increasing AFA concentrations and exposure time. Transcriptome analysis showed that AFA treatments induced additional stress responses in yeast cells compared to the control, shown by an up-regulation of stress-specific genes and a down-regulation of lipid biosynthesis, especially ergosterol. By documenting the detrimental effects associated with chemical AFA, we highlight the importance of developing innocuous systems for foam control in industrial fermentation processes.

Can human-like Bots control collective mood: agent-based simulations of online chats

International Nuclear Information System (INIS)

Tadić, Bosiljka; Šuvakov, Milovan

2013-01-01

Using an agent-based modeling approach, in this paper, we study self-organized dynamics of interacting agents in the presence of chat Bots. Different Bots with tunable ‘human-like’ attributes, which exchange emotional messages with agents, are considered, and the collective emotional behavior of agents is quantitatively analyzed. In particular, using detrended fractal analysis we determine persistent fluctuations and temporal correlations in time series of agent activity and statistics of avalanches carrying emotional messages of agents when Bots favoring positive/negative affects are active. We determine the impact of Bots and identify parameters that can modulate that impact. Our analysis suggests that, by these measures, the emotional Bots induce collective emotion among interacting agents by suitably altering the fractal characteristics of the underlying stochastic process. Positive emotion Bots are slightly more effective than negative emotion Bots. Moreover, Bots which periodically alternate between positive and negative emotion can enhance fluctuations in the system, leading to avalanches of agent messages that are reminiscent of self-organized critical states. (paper)

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

Science.gov (United States)

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Ion Channels Induced by Antimicrobial Agents in Model Lipid Membranes are Modulated by Plant Polyphenols Through Surrounding Lipid Media.

Science.gov (United States)

Efimova, Svetlana S; Zakharova, Anastasiia A; Medvedev, Roman Ya; Ostroumova, Olga S

2018-03-16

The potential therapeutic applications of plant polyphenols in various neurological, cardiovascular, metabolic and malignant disorders determine the relevance of studying the molecular mechanisms of their action on the cell membranes. Here, the quantitative changes in the physical parameters of model bilayer lipid membranes upon the adsorption of plant polyphenols were evaluated. It was shown that butein and naringenin significantly decreased the intrinsic dipole potential of cholesterol-free and cholesterol-enriched membranes. Cardamonin, 4'-hydroxychalcone, licochalcone A and liquiritigenin demonstrated the average efficiency, while resveratrol did not characterized by the ability to modulate the bilayer electrostatics. At the same time, the tested polyphenols affected melting of phospholipids with saturated acyl chains. The effects were attributed to the lipid disordering and a promotion of the positive curvature stress. According to DSC data and results of measurements of the threshold voltages that cause bilayer breakdown licochalcone A is the most effective agent. Furthermore, the role of the polyphenol induced changes in the electric and elastic properties of lipid host in the regulation of reconstituted ion channels was examined. The ability of the tested polyphenols to decrease the conductance of single ion channels produced by the antifungal cyclic lipopeptide syringomycin E was in agreement with their effects on the dipole potential of the lipid bilayers. The greatest effect of licochalcone A on the steady-state membrane conductance induced by the antifungal polyene macrolide antibiotic nystatin correlated with its greatest efficacy to induce the positive curvature stress. We also found that butein and naringenin bind specifically to a single pore formed by α-hemolysin from Staphylococcus aureus.

The role of antiseptic agents in atopic dermatitis.

Science.gov (United States)

Lee, Melissa; Van Bever, Hugo

2014-10-01

The skin of individuals with atopic dermatitis has a susceptibility to be colonized with Staphylococcus aureus. This has been associated with increased frequency and severity of exacerbations of atopic dermatitis. Therefore, there is a growing interest in the use of antiseptic agents to target primary bacterial colonization and infection. Antiseptic agents have been found to be better tolerated and less likely to induce bacterial resistance as compared to antibiotics. There is also a wide variety of antiseptic agents available. The efficacy of antiseptic agents has yet to be established as the studies reviewed previously have been small and of suboptimal quality. This review discusses the rationale behind targeting S. aureus with antiseptic agents and presents findings from a review of studies assessing the efficacy of antiseptics in atopic dermatitis in the last five years. Four studies were found, including a bleach bath study which has already been reviewed elsewhere. The remaining 3 studies assessed the efficacy of sodium hypochlorite containing cleansing body wash, sodium hypochlorite baths and 1% triclosan in leave on emollient. These studies suggested some benefit for the inclusion of antiseptic use with the mainstay management of atopic dermatitis, including a potential steroid sparring effect. However, there are many limitations to these studies which therefore warrant further investigation on the impact of antiseptic use in atopic dermatitis.

An adaptive response to alkylating agents in Aspergillus nidulans.

Science.gov (United States)

Hooley, P; Shawcross, S G; Strike, P

1988-11-01

A simple method is described for demonstrating adaptation to alkylation damage in Aspergillus nidulans. One wild type, two MNNG-sensitive, and one MNNG-resistant strain all showed improvement in colony growth when challenged with MNNG following appropriate inducing pretreatments. Other alkylating agents (MMS, EMS) could also adapt mycelium to later MNNG challenge, while 4NQO and UV could not. The inducible effect was not transmissible through conidia. A standard reversion assay based upon methG proved impractical for studying mutation frequencies during alkylation treatments owing to variations in MNNG resistance amongst revertants.

MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

Directory of Open Access Journals (Sweden)

Shuit-Mun Wong

Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

Energy Technology Data Exchange (ETDEWEB)

Langer, R.D., E-mail: rlanger@uaeu.ac.ae [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Lorke, D.E. [Florida International University, Miami, FL (United States); Neidl van Gorkom, K.F. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Petroianu, G. [Florida International University, Miami, FL (United States); Azimullah, S.; Nurulain, S.M.; Singh, S. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Fuchsjäger, M. [Al Ain Hospital, MUV-VAMED, Al Ain (United Arab Emirates)

2012-10-15

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

International Nuclear Information System (INIS)

Langer, R.D.; Lorke, D.E.; Neidl van Gorkom, K.F.; Petroianu, G.; Azimullah, S.; Nurulain, S.M.; Singh, S.; Fuchsjäger, M.

2012-01-01

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA

MRI observation of the light-induced release of a contrast agent from photo-controllable polymer micelles

International Nuclear Information System (INIS)

Lepage, Martin; Jiang Jinqiang; Babin, Jerome; Qi, Bo; Tremblay, Luc; Zhao Yue

2007-01-01

The encapsulation of molecules into nanocarriers is studied for its potential in delivering a high dose of anticancer drugs to a tumor, while minimizing side effects. Most systems either release their content in a non-specific manner or under specific environmental conditions such as temperature or pH. We have synthesized a novel class of photo-controllable polymer micelles that can stably encapsulate a hydrophilic compound and subsequently release it upon absorption of UV light. Here, we describe an in vitro magnetic resonance imaging assay that can evaluate the state of incorporation of a small Gd-based contrast agent. Our results indicate that the contrast agent alone can diffuse through a filter, but that the same agent incorporated into micelles cannot. After exposure to UV light, the micelles released the contrast agent, which could then diffuse through the filter. (note)

An Empirical Study of AI Population Dynamics with Million-agent Reinforcement Learning

OpenAIRE

Yang, Yaodong; Yu, Lantao; Bai, Yiwei; Wang, Jun; Zhang, Weinan; Wen, Ying; Yu, Yong

2017-01-01

In this paper, we conduct an empirical study on discovering the ordered collective dynamics obtained by a population of artificial intelligence (AI) agents. Our intention is to put AI agents into a simulated natural context, and then to understand their induced dynamics at the population level. In particular, we aim to verify if the principles developed in the real world could also be used in understanding an artificially-created intelligent population. To achieve this, we simulate a large-sc...

Efficacy of the chelating agent CaEDTA in reversing lead-induced changes in behavior.

Science.gov (United States)

Cory-Slechta, D A; Weiss, B

1989-01-01

The chelating agent CaEDTA has been reported to reverse the deficits in intellectual function and performance associated with Pb (lead) exposure in children. However, such studies have not included rigorous controls for the intervention procedures per se. The experiments reported here examined reversibility of performance changes in a rat model based on behavior sensitive to low-level Pb exposure. Rats were exposed to 50 ppm sodium or Pb acetate in drinking water from weaning. Performance maintained under a Fixed-Interval schedule of food reinforcement began at 55 days of age. Following the onset of the characteristic increase in short interresponse times (IRTs) associated with low-level Pb exposure after 35 experimental sessions, Pb treatment was terminated. Animals within both the control and Pb groups were then matched on the basis of performance indices and injected daily for 5 days with either saline, 75 mg/kg or 150 mg/kg CaEDTA. Subsequent changes in F1 performance were monitored for 35-60 sessions. No consistent effects of CaEDTA were detected in control animals. CaEDTA treatment failed to reverse the behavioral effects in Pb-exposed animals. If anything, it tended to further increase the proportion of short IRTs. These data suggest that better controlled clinical studies are warranted to evaluate the efficacy of CaEDTA in reversing Pb-induced behavioral effects before its application for these purposes becomes widespread.

Unusual expression of red fluorescence at M phase induced by anti-microtubule agents in HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci)

Energy Technology Data Exchange (ETDEWEB)

Honda-Uezono, Asumi [Section of Oral Radiation Oncology, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan); Section of Maxillofacial Surgery, Department of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan); Kaida, Atsushi [Section of Oral Radiation Oncology, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan); Michi, Yasuyuki; Harada, Kiyoshi [Section of Maxillofacial Surgery, Department of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan); Hayashi, Yoshiki; Hayashi, Yoshio [Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392 (Japan); Miura, Masahiko, E-mail: masa.mdth@tmd.ac.jp [Section of Oral Radiation Oncology, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549 (Japan)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Fucci visualizes cell cycle by green and red fluorescence. Black-Right-Pointing-Pointer Plinabulin, induced unusual red fluorescence at M-phase in HeLa-Fucci cells. Black-Right-Pointing-Pointer The unusual pattern was followed by mitotic catastrophe. Black-Right-Pointing-Pointer The unusual pattern may be an early indicator of cell death in HeLa cells. -- Abstract: Plinabulin (NPI-2358) is a novel microtubule-depolymerizing agent. In HeLa cells, plinabulin arrests the cell-cycle at M phase and subsequently induces mitotic catastrophe. To better understand the effects on this compound on the cell-cycle, we used the fluorescent ubiquitination-based cell cycle indicator (Fucci), which normally enables G1 and S/G2/M cells to emit red and green fluorescence, respectively. When HeLa-Fucci cells were treated with 50 nM plinabulin, cells began to fluoresce both green and red in an unusual pattern; most cells exhibited the new pattern after 24 h of treatment. X-irradiation efficiently induced G2 arrest in plinabulin-treated cells and significantly retarded the emergence of the unusual pattern, suggesting that entering M phase is essential for induction of the pattern. By simultaneously visualizing chromosomes with GFP-histone H2B, we established that the pattern emerges after nuclear envelope breakdown but before metaphase. Pedigree assay revealed a significant relationship between the unusual expression and mitotic catastrophe. Nocodazole, KPU-133 (a more potent derivative of plinabulin), and paclitaxel also exerted similar effects. From these data, we conclude that the unusual pattern may be associated with dysregulation of late M phase-specific E3 ligase activity and mitotic catastrophe following treatment with anti-microtubule agents.

Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

Directory of Open Access Journals (Sweden)

Meyerhoff James L

2011-07-01

Full Text Available Abstract Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus. Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There

Microencapsulation of self-healing agents containing a fluorescent dye

Directory of Open Access Journals (Sweden)

J. K. Lee

2013-01-01

Full Text Available Two different self-healing agent candidates, endo-dicyclopentadiene (endo-DCPD and 5-ethylidene-2-norbornene (ENB, containing a fluorescent dye surrounded by a melamine–urea–formaldehyde (MUF shell were microencapsulated by in-situ polymerization and the resulting microcapsules were characterized in this work. The microcapsules showed a narrow size distribution with a spherical shape and rough outer and smooth inner surfaces for both healing agent systems. Shell thicknesses of the microcapsules were ~880±80 nm for endo-DCPD and ~620±60 nm for ENB. The incorporation of a fluorescent dye as tracer into self-healing agents did not disturb the formation of microcapsules. The release of self-healing liquid into the induced crack from ruptured microcapsules in an epoxy coating layer was observed using a fluorescence microscopy. The use of a fluorescent dye is very effective in the observation of a damage site.

Arbuscular mycorrhizal fungi (AMF) as bio protector agents against wilt induced by Verticillium spp. in pepper

Energy Technology Data Exchange (ETDEWEB)

Goicoechea, N.; Garmendia, I.; Sanchez-Diaz, M.; Aguirreolea, J.

2010-07-01

Verticillium dahliae Kleb. is a vascular pathogen that alters water status and growth of pepper plants and causes drastic reductions in yield. Its control is difficult because it can survive in field soil for several years. The application of arbuscular mycorrhizal fungi (AMF) as bio protector agents against V. dahliae is an alternative to the use of chemicals which, in addition, is more respectful with the environment. The establishment of the mutualistic association of plant roots and AMF involves a continuous cellular and molecular dialogue between both symbionts that includes the pre activation of plant defense responses that may enhance the resistance or tolerance of mycorrhizal plants to soil-borne pathogens. Some AMF can improve the resistance of Capsicum annuum L. against V. dahliae. This is especially relevant for pepper cultivars (i.e. cv. Piquillo) that exhibit high susceptibility to this pathogen. Compared with non-mycorrhizal plants, mycorrhizal pepper can exhibit more balanced antioxidant metabolism in leaves along the first month after pathogen inoculation, which may contribute to delay both the development of disease symptoms and the decrease of photosynthesis in Verticillium-inoculated plants with the subsequent benefit for yield. In stems, mycorrhizal pepper show earlier and higher deposition of lignin in xylem vessels than non mycorrhizal plants, even in absence of the pathogen. Moreover, AMF can induce new isoforms of acidic chitinases and superoxide dismutase in roots. Mycorrhizal-specific induction of these enzymatic activities together with enhanced peroxidase and phenylalanine ammonia-lyase in roots may also be involved in the bio protection of Verticillium-induced wilt in pepper by AMF. (Author) 81 refs.

Improved success of sparse matrix protein crystallization screening with heterogeneous nucleating agents.

Directory of Open Access Journals (Sweden)

Anil S Thakur

2007-10-01

Full Text Available Crystallization is a major bottleneck in the process of macromolecular structure determination by X-ray crystallography. Successful crystallization requires the formation of nuclei and their subsequent growth to crystals of suitable size. Crystal growth generally occurs spontaneously in a supersaturated solution as a result of homogenous nucleation. However, in a typical sparse matrix screening experiment, precipitant and protein concentration are not sampled extensively, and supersaturation conditions suitable for nucleation are often missed.We tested the effect of nine potential heterogenous nucleating agents on crystallization of ten test proteins in a sparse matrix screen. Several nucleating agents induced crystal formation under conditions where no crystallization occurred in the absence of the nucleating agent. Four nucleating agents: dried seaweed; horse hair; cellulose and hydroxyapatite, had a considerable overall positive effect on crystallization success. This effect was further enhanced when these nucleating agents were used in combination with each other.Our results suggest that the addition of heterogeneous nucleating agents increases the chances of crystal formation when using sparse matrix screens.

Incorporating BDI Agents into Human-Agent Decision Making Research

Science.gov (United States)

Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

Chemical warfare agents.

Science.gov (United States)

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

Logics for Intelligent Agents and Multi-Agent Systems

NARCIS (Netherlands)

Meyer, John-Jules Charles

2014-01-01

This chapter presents the history of the application of logic in a quite popular paradigm in contemporary computer science and artificial intelligence, viz. the area of intelligent agents and multi-agent systems. In particular we discuss the logics that have been used to specify single agents, the

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Science.gov (United States)

Swami, Umang; Goel, Sanjay; Mani, Sridhar

2014-01-01

CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia is manageable, CPT-11 induced diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11 induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies, transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents. PMID:23597015

Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

Science.gov (United States)

Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

2015-09-01

The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

Sugammadex and rocuronium-induced anaphylaxis.

Science.gov (United States)

Takazawa, Tomonori; Mitsuhata, Hiromasa; Mertes, Paul Michel

2016-04-01

Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.

Biological Agents

Science.gov (United States)

... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

related apoptosis-inducing ligand in transplastomic tobacco

African Journals Online (AJOL)

-inducing ligand (sTRAIL) can, as the whole length TRAIL protein, bind with its receptors and specifically induce the apoptosis of cancer cells; therefore, it has been developed as a potential therapeutic agent for various cancer treatments.

[Complications due to contrast agent administration: what has been confirmed in prevention?].

Science.gov (United States)

Schönenberger, E; Mühler, M; Dewey, M

2010-12-01

Computed tomography (CT) and magnetic resonance imaging (MRI) have been evaluated by internists to be the most important medical innovations. Often, intravenous contrast agent administration is required for answering the clinical questions to CT and MRI. In this review we present an overview of the most common and most important aspects that need to be considered prior to intravenous contrast agent administration. We discuss aspects of renal impairment (contrast-induced nephropathy, nephrogenic systemic fibrosis), allergy-like reactions, hyperthyroidism, and pregnancy and breast-feeding.

Study of new 113mIn-BAT complexes for myocardial imaging agents

International Nuclear Information System (INIS)

Zhu Lin; Liu Boli; Kojima, M.

1991-01-01

Some new BAT derivatives are designed and synthesized in order to find some ideal myocardial imaging agents. These ligands form pentacoordinated complexes with indium cation. The structures of ligand BAT-TE and complexes In-BAT-TE and In-BAT-ETE are determined by X-ray crystallography at first. Biodistribution shows that the higher lipophilicity of complex induces apparently higher myocardial accumulation. Up to date, complex B is the best 113m In-labeled myocardial imaging agent. It is also suited to 111 In

Evaluation of the cytotoxicity of dihydroxytryptamines and 5-hydroxytryptamine antagonists as cytotoxic agents in dimethylhydrazine-induced adenocarcinomata.

Science.gov (United States)

Tutton, P J; Barkla, D H

1978-01-01

The cytotoxicity of 5,6-dihydroxytryptamine (5,6-DHT), 5,7-dihydroxytryptamine (5,7-DHT), bromolysergic acid diethylamide (BOL), methysergide, and cyproheptadine, and also of 5,6-DHT together with either BOL, methysergide, or cyproheptadine in dimethylhydrazine-induced (DMH) carcinomata of rat colon was evaluated by estimating the percentage of necrotic cells in histological sections of tissues taken 15 h after injection of each of the drugs. In addition, the influence of methysergide and cyproheptadine on the tumour cell mitotic rate was estimated by means of a stathmokinetic technique. Both 5,6-DHT and 5,7-DHT were cytotoxic at each dose tested and for each of these agents the percentage of necrotic cells was directly correlated with the dose of drug used. BOL was not found to be cytotoxic to the colonic carcinomata, whereas both methysergide and cyproheptadine did cause detectable tumour cell necrosis. Methysergide was also found to accelerate tumour cell proliferation, whereas cyproheptadine did not. BOL competitively inhibited the cytotoxicity of 5,6-DHT and neither methysergide nor cyproheptadine potentiated the effect of 5,6 DHT.

Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

Directory of Open Access Journals (Sweden)

Sachiko Ezoe

2012-07-01

Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

Photo-induced reduction of flavin mononucleotide in aqueous solutions

International Nuclear Information System (INIS)

Song, S.-H.; Dick, B.; Penzkofer, A.

2007-01-01

The photo-induced reduction of flavin mononucleotide (FMN) in aqueous solutions is studied by absorption spectra measurement under aerobic and anaerobic conditions. Samples without exogenous reducing agent and with the exogenous reducing agents ethylene-diamine-tetraacetic acid (EDTA) and dithiothreitol (DTT) are investigated. Under anaerobic conditions the photo-induced reduction with and without reducing agents is irreversible. Under aerobic conditions the photo-reduction without added reducing agent is small compared to the photo-degradation, and the photo-reduction of FMN by the reducing agents is reversible (re-oxidation in the dark). During photo-excitation of FMN the dissolved oxygen is consumed by singlet oxygen formation and subsequent chemical reaction. After light switch-off slow re-oxidation (slow absorption recovery) occurs due to air in-diffusion from surface. EDTA degradation by FMN excitation leads to oxygen scavenging. The quantum efficiencies of photo-reduction under aerobic and anaerobic conditions are determined. The re-oxidation of reduced FMN under aerobic conditions and due to air injection is investigated

HIV transcription is induced with some forms of cell killing

International Nuclear Information System (INIS)

Woloschak, G.E.; Schreck, S.; Chang-Liu, C.-M.; Libertin, C.R.

1996-01-01

Using HeLa cells stably transfected with an HIV-LTR-CAT construct', we demonstrated a peak in CAT induction that occurs in viable (but not necessarily cell-division-competent) cells 24 h following exposure to some cell-killing agents. Γ rays were the only cell-killing agent which did not induce HIV transcription; this can be attributed to the fact that γ-ray-induced apoptotic death requires function p53, which is missing in HeLa cells. For all other agents, HIV-LTR induction was dose-dependent and correlated with the amount of cell killing that occurred in the culture

Fixed drug eruption induced by an iodinated non-ionic X-ray contrast medium: a practical approach to identify the causative agent and to prevent its recurrence

Energy Technology Data Exchange (ETDEWEB)

Boehm, Ingrid; Block, Wolfgang; Schild, Hans H. [University of Bonn, Department of Radiology, Bonn (Germany); Medina, Jesus; Prieto, Pilar [JUSTESA IMAGEN SA, Biological R and D Department, Madrid (Spain)

2007-02-15

We describe the case of a 61-year-old physician who developed a fixed drug eruption (FDE) after i.v. administration of a non-ionic monomeric iodinated X-ray contrast medium (CM) (iopromide). During CM injection, a sensation of heat occurred, which was most intense in the right inguinal region. Four hours later, the FDE arose with a red macule of approximately 2 cm in diameter covering a dermal infiltration in the right inguinal region, and enlarged up to a final size of 15 x 8 cm, accompanied by a burning sensation. The patient's history revealed a similar reaction in the same localization and of the same clinical appearance after CM injection 1 year before. Patch testing 4 months later revealed positive reactions to iomeprol and iohexol. Iopamidol injection for another CT examination 23 months later was well tolerated. Based on these results, we suggest patch testing after CM-induced FDE, which could help to select a CM for future CT examinations. Late onset of adverse CM reactions may manifest as FDE. Patch testing within the previous skin reaction area is the diagnostic tool that should be used to confirm the suspected agent, possible cross-reacting agents and well-tolerated agents. (orig.)

Fixed drug eruption induced by an iodinated non-ionic X-ray contrast medium: a practical approach to identify the causative agent and to prevent its recurrence

International Nuclear Information System (INIS)

Boehm, Ingrid; Block, Wolfgang; Schild, Hans H.; Medina, Jesus; Prieto, Pilar

2007-01-01

We describe the case of a 61-year-old physician who developed a fixed drug eruption (FDE) after i.v. administration of a non-ionic monomeric iodinated X-ray contrast medium (CM) (iopromide). During CM injection, a sensation of heat occurred, which was most intense in the right inguinal region. Four hours later, the FDE arose with a red macule of approximately 2 cm in diameter covering a dermal infiltration in the right inguinal region, and enlarged up to a final size of 15 x 8 cm, accompanied by a burning sensation. The patient's history revealed a similar reaction in the same localization and of the same clinical appearance after CM injection 1 year before. Patch testing 4 months later revealed positive reactions to iomeprol and iohexol. Iopamidol injection for another CT examination 23 months later was well tolerated. Based on these results, we suggest patch testing after CM-induced FDE, which could help to select a CM for future CT examinations. Late onset of adverse CM reactions may manifest as FDE. Patch testing within the previous skin reaction area is the diagnostic tool that should be used to confirm the suspected agent, possible cross-reacting agents and well-tolerated agents. (orig.)

Recent developments in antiviral agents against enterovirus 71 infection.

Science.gov (United States)

Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

2014-02-12

Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

Differential response of biochemical parameters to EMS and MMS treatments and their dose effect relationship on chromosomes in induced diabetic mouse

Directory of Open Access Journals (Sweden)

B.B.D. Khalandar

2015-10-01

Conclusion: (1 Even though alkylating agents induce chromosomal aberrations in diabetic mice, MMS, a methylating agent is a more potent inducer of chromatid type of aberrations than EMS, an ethylating agent. (2 Diabetic mouse is more resistant than the non diabetic to alkylating agents and (3 the tested agents altered the analyzed biochemical parameters.

Radioprotection: mechanism and radioprotective agents including honeybee venom

Energy Technology Data Exchange (ETDEWEB)

Varanda, E.A.; Tavares, D.C. [UNESP, Araraquara, SP (Brazil). Escola de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas

1998-07-01

Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

Radioprotection: mechanism and radioprotective agents including honeybee venom

International Nuclear Information System (INIS)

Varanda, E.A.; Tavares, D.C.

1998-01-01

Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

E. coli mismatch repair enhances AT-to-GC mutagenesis caused by alkylating agents.

Science.gov (United States)

Nakano, Kota; Yamada, Yoko; Takahashi, Eizo; Arimoto, Sakae; Okamoto, Keinosuke; Negishi, Kazuo; Negishi, Tomoe

2017-03-01

Alkylating agents are known to induce the formation of O 6 -alkylguanine (O 6 -alkG) and O 4 -alkylthymine (O 4 -alkT) in DNA. These lesions have been widely investigated as major sources of mutations. We previously showed that mismatch repair (MMR) facilitates the suppression of GC-to-AT mutations caused by O 6 -methylguanine more efficiently than the suppression of GC-to-AT mutations caused by O 6 -ethylguanine. However, the manner by which O 4 -alkyT lesions are repaired remains unclear. In the present study, we investigated the repair pathway involved in the repair of O 4 -alkT. The E. coli CC106 strain, which harbors Δprolac in its genomic DNA and carries the F'CC106 episome, can be used to detect AT-to-GC reverse-mutation of the gene encoding β-galactosidase. Such AT-to-GC mutations should be induced through the formation of O 4 -alkT at AT base pairs. As expected, an O 6 -alkylguanine-DNA alkyltransferase (AGT) -deficient CC106 strain, which is defective in both ada and agt genes, exhibited elevated mutant frequencies in the presence of methylating agents and ethylating agents. However, in the UvrA-deficient strain, the methylating agents were less mutagenic than in wild-type, while ethylating agents were more mutagenic than in wild-type, as observed with agents that induce O 6 -alkylguanine modifications. Unexpectedly, the mutant frequencies decreased in a MutS-deficient strain, and a similar tendency was observed in MutL- or MutH-deficient strains. Thus, MMR appears to promote mutation at AT base pairs. Similar results were obtained in experiments employing double-mutant strains harboring defects in both MMR and AGT, or MMR and NER. E. coli MMR enhances AT-to-GC mutagenesis, such as that caused by O 4 -alkylthymine. We hypothesize that the MutS protein recognizes the O 4 -alkT:A base pair more efficiently than O 4 -alkT:G. Such a distinction would result in misincorporation of G at the O 4 -alkT site, followed by higher mutation frequencies in wild

Frequency and spectrum of chlorophyll-deficient mutations in rice after treatment with radiation and alkylating agents

International Nuclear Information System (INIS)

Bhan, A.K.; Kaul, M.L.H.

1976-01-01

Three varieties of rice were treated with gamma rays and two alkylating agents EMS and DES, separately and in combinations, with a view to finding out the frequency and spectrum of chlorophyll mutations in relation to the genotype and the nature of the mutagen. Chlorophyll mutation frequency was enhanced with increasing dose but dropped at very high doses (doses that induced over 90% seeding lethality in M 1 ). The fall was attributed to either the increased mutated sector and diplontic selection after exposure to very high doses or relatively high resistance of some of the seeds. Among chlorophyll mutants in M 2 induced by radiations as well as alkylating agents, the albina type formed the majority class. EMS induced a significantly higher proportion of albinas than did gamma rays

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

International Nuclear Information System (INIS)

Liu, Zhiguo; Wang, Yi; Sun, Yusheng; Ren, Luqing; Huang, Yi; Cai, Yuepiao; Weng, Qiaoyou; Shen, Xueqian; Li, Xiaokun; Liang, Guang

2013-01-01

Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy. A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated. B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo. A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC

The effects of X-ray energy and an iodine-based contrast agent on chromosome aberrations

International Nuclear Information System (INIS)

Matsubara, Sho; Kubota, Nobuo; Katoh, Tsuguhisa; Yoshino, Norio; Sasaki, Takehito; Sasaki, Masao S.

1994-01-01

A study was undertaken to evaluate the effect of combining irradiation with X rays of various energies and an iodine-based contrast agent on the induction of chromosome aberrations in the peripheral lymphocytes of blood samples taken from healthy young donors. Although no enhancement of the effect of radiation was induced when blood samples with the iodine-based contrast agent were given 35 kV X irradiation, an 80 kV X-ray exposure induced an enhanced level of chromosome aberrations, and a 250 kV X irradiation, an enhancement of the frequencies of chromosome aberrations was seen in blood samples with the iodine-based contrast agent, especially when a Lucite phantom was employed in studies to increase the scattered rays. It was thus shown by microdosimetric analysis that X irradiation combined with an iodine-based contrast agent causes an enhancement of the absorbed radiation dose, which is dependent on the X-ray energies employed. This phenomenon may have clinical use in the radiotherapeutic management of tumors, although further extensive studies of tumor vascularity must be pursued before this can be applied clinically. 21 refs., 8 figs., 3 tabs

Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury.

Science.gov (United States)

Milatovic, Dejan; Gupta, Ramesh C; Yu, Yingchun; Zaja-Milatovic, Snjezana; Aschner, Michael

2011-11-01

Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (pprotected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F(2)-IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100mg/kg, s.c.) 24h. Additionally, pretreatment with vitamin E (100mg/kg, i.p.) or ibuprofen (140 μg/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F(2)-IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional dopaminergic transmission and slowing of the progression of Mn-induced neurodegenerative processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent

International Nuclear Information System (INIS)

Bettmann, M.A.; Bourdillon, P.D.; Barry, W.H.; Brush, K.A.; Levin, D.C.

1984-01-01

The effects on cardiac hemodynamics and of a standard contrast agent, sodium methylglucamine diatrizoate [Renografin 76] were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patietns undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk

TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

Science.gov (United States)

Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

2008-09-01

We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

New cancer cells apoptosis agents: Fluorinated aza-heterocycles

Science.gov (United States)

Prima, D. O.; Baev, D. S.; Vorontsova, E. V.; Frolova, T. S.; Bagryanskaya, I. Yu.; Slizhov, Yu. G.; Tolstikova, T. G.; Makarov, A. Yu.; Zibarev, A. V.

2017-09-01

Fluorinated benzo-fused 1,3-diazoles, 1,2,3-triazoles, 1,2,5-thia/selenadiazoles and 1,4-diazines were synthesized and tried for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma) cells. The diazoles, triazoles and selenadiazoles were cytotoxic with IC50 = 2.2-26.4 µM and induced the cells apoptosis at concentrations C = 1-25 µM. At the same time, they were nontoxic towards normal cells. Due to this, these scaffolds were used in the computer-aided molecular design of new antitumor agents. Particularly, novel 1,2,3-triazole and 1,3-diazole derivatives for the binding site of the PAS domain of the transcription factor HIF were designed and some of them synthesized for further study. Overall, new anticancer agents featuring apoptotic activity are suggested.

The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

NARCIS (Netherlands)

van Roosmalen, Ingrid A. M.; Dos Reis, Carlos R; Setroikromo, Rita; Yuvaraj, Saravanan; Joseph, Justin V.; Tepper, Pieter G.; Kruyt, Frank A. E.; Quax, Wim J.

2014-01-01

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related

Budget impact analysis on erythropoiesis-stimulating agents use for the management of chemotherapy-induced anaemia in Greece.

Science.gov (United States)

Nikolaidi, Eleftheria; Hatzikou, Magdalini; Geitona, Mary

2013-07-16

Chemotherapy-induced anaemia is a common and significant complication of chemotherapy treatment. Blood transfusion and administration of Erythropoiesis-Stimulating Agents (ESAs) either alone or in combination with iron are the most widely used therapeutic options. In Greece, ESAs are among the top ten therapeutic groups with the highest pharmaceutical expenditure, since they are fully reimbursed by social security funds. The objective of the study is to determine potential cost savings related with the use of biosimilar over originator ESAs for the management of the newly diagnosed chemotherapy-induced anemic patients. A budget impact analysis has been carried through the elaboration of national epidemiological, clinical and economic data. Epidemiological data derived from WHO (GLOBOCAN) and the European Cancer Anaemia Survey. Clinical data reflect oncology patients' disease management. ESAs consumption was based on data from the biggest social security fund (IKA). The administration of ESAs under different dosing schemes and time periods has been estimated by separating them in originators and biosimilars as well as by classifying anaemic patients in responders and non-responders. Cost analysis is based on newly diagnosed patients' alternative treatment scenarios. Treatment costs and prices are used in 2012 values. The Social Security Funds's perspective was undertaken. Based on the annual incidence rates, 2.551 newly diagnosed chemotherapy-induced anemic patients are expected to be treated with ESAs. Average cost of treatment on originators ESAs for responders is €2.887 for the 15-week ESAs treatment and €5.019 for non-responders, while on biosimilars €2.623 and €4.009 respectively. Treatment cost on biosimilars is 10.1% lower than originators for responders and 25.2% for non-responders. Budget impact estimates show that treating anemic patients with originator ESAs was estimated at €10.084.800 compared to €8.460.119 when biosimilar ESAs were used

Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells.

Science.gov (United States)

Riaz Ahmed, Kausar Begam; Kanduluru, Ananda Kumar; Feng, Li; Fuchs, Philip L; Huang, Peng

2017-05-01

Metastatic melanoma is the most aggressive of all skin cancers and is associated with poor prognosis owing to lack of effective treatments. 25-epi Ritterostatin GN1N is a novel antitumor agent with yet undefined mechanisms of action. We sought to delineate the antitumor mechanisms of 25-epi Ritterostatin GN1N in melanoma cells to determine the potential of this compound as a treatment for melanoma. Activation of the endoplasmic reticulum (ER) stress protein glucose-regulated protein 78 (GRP78) has been associated with increased melanoma progression, oncogenic signaling, drug resistance, and suppression of cell death. We found that 25-epi Ritterostatin GN1N induced cell death in melanoma cells at nanomolar concentrations, and this cell death was characterized by inhibition of GRP78 expression, increased expression of the ER stress marker CHOP, loss of mitochondrial membrane potential, and lipidation of the autophagy marker protein LC3B. Importantly, normal melanocytes exhibited limited sensitivity to 25-epi Ritterostatin GN1N. Subsequent in vivo results demonstrated that 25-epi Ritterostatin GN1N reduced melanoma growth in mouse tumor xenografts and did not affect body weight, suggesting minimal toxicity. In summary, our findings indicate that 25-epi Ritterostatin GN1N causes ER stress and massive autophagy, leading to collapse of mitochondrial membrane potential and cell death in melanoma cells, with minimal effects in normal melanocytes. Thus, 25-epi Ritterostatin GN1N is a promising anticancer agent that warrants further investigation.

Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

Science.gov (United States)

Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

2016-01-01

Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

Temozolomide-Induced Myelodysplasia

Directory of Open Access Journals (Sweden)

Ethan A. Natelson

2010-01-01

Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

Energy Technology Data Exchange (ETDEWEB)

Rodriguez R, R.; Huerta V, C.; MOrales R, P.R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

Energy Technology Data Exchange (ETDEWEB)

Rodriguez R, R; Huerta V, C; MOrales R, P R [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

2006-07-01

The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2013-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

A Composite Agent Architecture for Multi-Agent Simulations

OpenAIRE

VanPutte, Michael; Osborn, Brian; Hiles, John

2002-01-01

CGF Computer Generated Forces and Behavioral Representation The MOVES Institute’s Computer-Generated Autonomy Group has focused on a research goal of modeling complex and adaptive behavior while at the same time making the behavior easier to create and control. This research has led to several techniques for agent construction, that includes a social and organization relationship management engine, a composite agent architecture, an agent goal apparatus, a structure for capturi...

99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

Science.gov (United States)

Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

2017-05-15

The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

TACtic- A Multi Behavioral Agent for Trading Agent Competition

Science.gov (United States)

Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

Prevention and Treatment of Vaginal Bleeding after Drug-induced Abortion by Yaoliuan Capsule and Its Effects on Menses Recovery

Institute of Scientific and Technical Information of China (English)

JIN Zhichun; HUANG Guangying

2005-01-01

Summary: In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period ≤ 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8 %) of complete abortion, 7 cases (4.2 %) of incomplete abortion; In the control group, there were 146 cases (94.2 %) of complete abortion, 6 cases (3.9 %) of incomplete abortion, 3 cases (1.9 %) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5±5.2 days and 33.8 d±8.6 days respectively in study and control groups. The menstrual period was 6.1±3.5 days and 9.9±5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.

Iodinated contrast agent-induced nephropathy

International Nuclear Information System (INIS)

Erley, C.

2007-01-01

Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management. A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.). (orig.) [de

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Directory of Open Access Journals (Sweden)

Donghee Park

Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Science.gov (United States)

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the