Suramin inhibits DNA damage in human prostate cancer cells treated with topoisomerase inhibitors in vitro

Suramin, a highly sulfonated drug, has been reported to be effective against several human malignancies in vitro and in vivo, and currently is undergoing clinical trials against prostate tumors. The biochemical and molecular mechanisms for suramin's antiproliferative activity are not clear. In order to define the biochemical basis for its antitumor activity and to enhance suramin's chemotherapeutic potential while decreasing its toxicity, we have examined interactions of suramin with topoisomerase I and 11 and several clinically active anticancer drugs against the human prostate (PC3 and LNCaP) cancer cell line. While etoposide, m-AMSA, camptothecin, and SN-38 (the active metabolite of CPT-11) were active in killing prostate cells as single agents, combinations of suramin and these agents were antagonistic against these cells. We found that suramin inhibited activities of purified topoisomerase I and II in vitro as measured by relaxation and cleavage assays. Further studies indicated that suramin also inhibited the drug-induced DNA damage in vitro and in isolated nuclei. These findings indicate that combinations of suramin with topoisomerase inhibitors, for example, VP-16, m-AMSA, or CPT, may not be beneficial to patients receiving suramin-containing chemotherapy. © 1993 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America

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Family welfare

Between 1901-1921, India gained 12.9 million people because mortality remained high. The death rate fell between 1921-1951, but birth rates remained the same. Therefore 110 million people were added--2 times the population increase between 1891-1921. Between 1951-1981, the population increased to 324 million. Socioeconomic development was responsible for most of the downward trend in the birth rate during the 20th century. Even though large families were the norm in early India, religious leaders encouraged small family size. The 1st government family planning clinics in the world opened in Mysore and Bangalore in 1930. Right before Independence, the Bhore Committee made recommendations to reduce population growth such as increasing the age of marriage for girls. Since 1951 there has been a change in measures and policies geared towards population growth with each of the 7 5-Year Plans because policy makers applied what they learned from each previous plan. The 1st 5-Year Plan emphasized the need to understand what factors contribute to population growth. It also integrated family planning services into health services of hospitals and health centers. The government was over zealous in its implementation of the sterilization program (2nd 5-Year Plan, 1956-1961), however, which hurt family planning programs for many years. As of early 1992, sterilization, especially tubectomy, remained the most popular family planning method, however. The 7th 5-Year Plan changed its target of reaching a Net Reproductive Rate of 1 by 2001 to 2006-2011. It set a goal of 100% immunization coverage by 1990 but it did not occur. In 1986, the Ministry of Health and Family Welfare planned to make free contraceptives available in urban and rural areas and to involve voluntary organizations. The government needs to instill measures to increase women's status, women's literacy, and age of marriage as well as to eliminate poverty, ensure old age security, and ensure child survival and development.     

Ochratoxin a production in Bavarian cereal grains stored at 15 and 19% moisture content

Wheat, barley, and maize, each in 15-kg parcels at 15 and 19% initial moisture content (IMC), were kept in a Bavarian farm granary from June through November 1990. During this period, the grain at each IMC was analyzed for mycotoxins and monitored for grain temperature, carbon dioxide, seed germination, and microfloral incidence and abundance. Barley and maize stored for 20 weeks at 19% IMC contained ochratoxin A in amounts of 70 and 90 g/kg, respectively. This mycotoxin was not detected in wheat stored at 19% IMC, nor in the grains stored at 15% IMC. Aflatoxin B₁, sterigmatocystin, citrinin, and zearalenone were also assayed but not detected in grains stored at either IMC. Principal component analysis of the data indicated that ochratoxin A was produced in a damp niche in maize, when abundant metabolic activity and CO₂ production by Penicillium glandicola and Aspergillus spp. were common.Contribution No. 1476 of the Agriculture Canada Research Station.     

Tumorigenesis of mammary gland by 7,12-dimethylbenz(a)anthracene during pregnancy: relationship with DNA synthesis

The relationship between mammary cell proliferation during pregnancy and susceptibility to 7,12-dimethylbenz(a)anthracene (DMBA) was examined. DMBA was administered intravenously to Sprague-Dawley rats on the 5th, 10th or 15th day of pregnancy. [3H]thymidine labelling index (LI) of the mammary cells at the time of treatment with the carcinogen was determined and found to be higher in the pregnant rats than in age-matched virgin controls. In spite of the high proliferative index of the mammary cells, significant inhibition of tumorigenesis occurred in the pregnancy rats allowed to complete pregnancy and parturition following treatment with DMBA. However, when pregnancy was terminated by cesarian section shortly after treatment with DMBA, there was a significantly higher tumor incidence as compared to the "full-term" rats. It was observed that the earlier the pregnancy was terminated, the greater was the incidence of mammary tumors. This would indicate that the inhibitory effect of pregnancy is related to changes occurring during the later half of gestation. The differentiation of mammary cells for milk synthesis as pregnancy progresses is postulated to be a major reason for the observed refractoriness of the mammary cells to DMBA at that time.     

Microbially triggered drug delivery to the colon.

Increasing acceptance of protein- and peptide-based drugs necessitates an investigation into the suitability of various sites for their administration. Colon is being investigated for delivery of such molecules. Colon-specific drug delivery is designed to target drug molecules specifically to this area. Development of site-specific delivery systems may exploit a specific property of the target site for drug activation/release. The gastrointestinal tract is inhabited by over 400 bacterial species, each having a specific niche in the tract. Colon, the distal part of the intestine is inhabited by a large variety of gram negative microflora. This flora produces a vast number of enzymes which are being exploited for formulation of colon-specific drug delivery systems. A number of microbially activated systems for colon-specific drug delivery are being evaluated. These include prodrugs and synthetic or natural polymer-based delivery systems. This article aims at reviewing the various microbially activated drug delivery systems for colon-specific drug delivery with specific reference to the microflora of the various segments of the gastrointestinal tract and their role in targeting drug delivery to the colon.     

The influence of reported paternal attitudes on the decision to breast-feed

Objective: To identify factors that influence a woman's decision to breast-feed.
Methodology: Five hundred and fifty-six women were recruited from the maternity wards of two Perth hospitals. Data were collected from a self-administered questionnaire completed by participants prior to discharge. Logistic regression analysis was used to determine factors influencing the initiation of breast-feeding.
Results: At discharge from hospital 83.8% of women were breast-feeding, including 6% who were giving complementary formula feeds. After controlling for potentially confounding demographic and biomedical factors, the father's reported preference for breast-feeding was found to be the most important factor influencing a woman's decision to breast-feed (OR 10.18).
Conclusion: Fathers participate in and influence the choice of infant feeding method and should be included in breast-feeding discussions.     

Margin of safety for discharge after apnea in preterm infants

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at 相似文献