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1.
Title: Role of the calcium channel in blastocyst implantation: a novel contraceptive target.
Author: Banerjee A; Padh H; Nivsarkar M
Source: Journal of Basic and Clinical Physiology and Pharmacology. 2009;20(1):43-53.
Abstract: The proinflammatory blastocyst implantation cascade involves important mediators like prostaglandins (PG). The influx of calcium via the calcium channel acts as a trigger for the activation of the PG synthesis pathway. Hence, it was hypothesized that calcium channel blockers that are known to possess anti-inflammatory activity may interfere with normal implantation. Pregnant Swiss albino mice (Mus musculus) were treated with diltiazem (1) 4 mg/kg, po on days 1-6 of pregnancy, n=6/day) or (2) at the implantation site (25 microg/animal) via intrauterine injection in the right horn at 5:00 pm on day 4. The intact uterus was used to assay lipid peroxidation and superoxide dismutase activity as markers of membrane fluidity or to observe the day 15 fetus. Oral diltiazem treatment in therapeutic dosage before and during the implantation period did not cause any change in normal uterine milieu during the window of implantation. When injected into the uterine lumen 12-14 h before the average implantation time, however, a complete failure in implantation was observed. Thus, the site specific action of diltiazem may be blocking prostaglandin synthesis, hence causing implantation failure. Oral diltiazem treatment did not mimic this action, indicating that although orally safe in pregnancy in therapeutic dosage, calcium channel blockers may provide a new and yet unknown target in female contraceptive research.
Language: English
Keywords:
INDIA | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY PROCEDURES | LABORATORY ANIMALS | LIPID METABOLIC EFFECTS | CONTRACEPTION RESEARCH | Asia, Southern | Asia | Developing Countries | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Lipids | Physiology | Biology | Contraception | Family Planning
Document Number: 342045

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Peer Reviewed

Title: Interaction of contraceptive antimicrobial peptide nisin with target cell membranes: implications for use as vaginal microbicide.
Author: Gupta SM; Aranha CC; Bellare JR; Reddy KV
Source: Contraception. 2009 Sep;80(3):299-307.
Abstract: BACKGROUND: Nisin, a naturally occurring antimicrobial peptide (AMP), is currently the focus of clinical trials as an intravaginal microbicide. Therefore its mechanism of interaction with various cell membranes was studied. STUDY DESIGN: Flow cytometry was used for quantitative estimation of membrane damage by nisin which was further determined by scanning electron microscopy (SEM). Affinity of nisin for different unilamellar liposome vesicles was determined spectroflurometrically and confirmed using laser scanning confocal microscopy (LSCM). RESULTS: Propidium iodide (PI) staining by flow cytometry exhibited selective membrane permeabilizing effect of nisin on sperm and bacterial membranes which correlated with ultrastructural changes. In vitro interaction of nisin with liposome model vesicles revealed significant leakage of calcein from liposomes composed of phosphatidylcholine/phosphatidylglycerol (POPC/POPG) (e.g., bacteria) and phosphatidylcholine/phosphatidylserine (POPC/POPS) (e.g., spermatozoa) as compared to phosphatidylcholine/phosphatidylethanolamine (POPC/POPE) vesicles (e.g., red blood corpuscles). LSCM results were in complete agreement with cell membrane affinity studies. CONCLUSION: This unique property of nisin can be exploited in the development of a safe and effective vaginal microbicide for the prevention of sexually transmitted infections/acquired immunodeficiency syndrome (STIs/AIDS) and unplanned pregnancies.
Language: English
Keywords:
INDIA | RESEARCH REPORT | QUANTITATIVE RESEARCH | CLINICAL TRIALS | LABORATORY ANIMALS | SPERMATOZOA | IN VITRO | MICROBICIDES | AIDS PREVENTION | SEXUALLY TRANSMITTED DISEASES | PREGNANCY, UNPLANNED | PROGRAM EVALUATION | Asia, Southern | Asia | Developing Countries | Research Methodology | Clinical Research | Germ Cells | Genitalia | Urogenital System | Physiology | Biology | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | AIDS | HIV Infections | Viral Diseases | Diseases | Reproductive Tract Infections | Infections | Reproductive Behavior | Fertility | Population Dynamics | Demographic Factors | Population | Programs | Organization and Administration
Document Number: 342572

Peer Reviewed

Title: Preclinical characterization of a (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide: a selective androgen receptor modulator for hormonal male contraception.
Author: Jones A; Chen J; Hwang DJ; Miller DD; Dalton JT
Source: Endocrinology. 2009 Jan;150(1):385-95.
Abstract: The pharmacologic effects of (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) were characterized in male rats as an animal model of hormonal male contraception. S-23 showed high binding affinity (inhibitory constant = 1.7 +/- 0.2 nm) and was identified as a full agonist in vitro. In castrated male rats, the ED50 of S-23 in the prostate and levator ani muscle was 0.43 and 0.079 mg/d, respectively. In intact male rats treated for 14 d, S-23 alone suppressed LH levels by greater than 50% at doses greater than 0.1 mg/d, with corresponding decreases in the size of the prostate but increases in the size of levator ani muscle. In intact male rats treated for up to 10 wk with S-23 and estradiol benzoate (EB; necessary to maintain sexual behavior in rats), S-23 showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of LH and FSH. EB alone showed no effect on spermatogenesis. In the EB + S-23 (0.1 mg/d) group, four of six animals showed no sperm in the testis and zero pregnancies (none of six) in mating trials. After termination of treatment, infertility was fully reversible, with a 100% pregnancy rate observed after 100 d of recovery. S-23 increased bone mineral density and lean mass but reduced fat mass in a dose-dependent manner. This is the first study to show that a selective androgen receptor modulator combined with EB is an effective and reversible regimen for hormonal male contraception in rats. The beneficial effects of S-23 on the muscle, tissue selectivity, and favorable pharmacokinetic properties make it a strong candidate for use in oral male contraception.
Language: English
Keywords:
UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL RESEARCH | ANIMALS | LABORATORY ANIMALS | MALE CONTRACEPTION | HORMONE ANTAGONISTS | REVERSIBILITY | CONTRACEPTION RESEARCH | Developed Countries | North America | Americas | Research Methodology | Natural Resources | Environment | Contraception | Family Planning | Hormones | Endocrine System | Physiology | Biology
Document Number: 330565

4.
Title: Testicular cell junction: a novel target for male contraception.
Author: Lee NP; Wong EW; Mruk DD; Cheng CY
Source: Current Medicinal Chemistry. 2009;16(7):906-15.
Abstract: Even though various contraceptive methods are widely available, the number of unwanted pregnancies is still on the rise in developing countries, pressurizing the already resource limited nations. One of the major underlying reasons is the lack of effective, low cost, and safe contraceptives for couples. During the past decade, some studies were performed using animal models to decipher if the Sertoli-germ cell junction in the testis is a target for male fertility regulation. Some of these study models were based on the use of hormones and/or chemicals to disrupt the hypothalamic-pituitary-testicular axis (e.g., androgen-based implants or pills) and others utilized a panel of chemical entities or synthetic peptides to perturb spermatogenesis either reversibly or non-reversibly. Among them, adjudin, a potential male contraceptive, is one of the compounds exerting its action on the unique adherens junctions, known as ectoplasmic specializations, in the testis. Since the testis is equipped with inter-connected cell junctions, an initial targeting of one junction type may affect the others and these accumulative effects could lead to spermatogenic arrest. This review attempts to cover an innovative theme on how male infertility can be achieved by inducing junction instability and defects in the testis, opening a new window of research for male contraceptive development. While it will still take much time and effort of intensive investigation before a product can reach the consumable market, these findings have provided hope for better family planning involving men.
Language: English
Keywords:
CHINA | LITERATURE REVIEW | CLINICAL RESEARCH | LABORATORY ANIMALS | MEN | TESTIS | CONTRACEPTIVE AGENTS, MALE | SPERMATOGENESIS BLOCKING AGENTS | CYTOLOGIC EFFECTS | Asia, Eastern | Asia | Developing Countries | Research Methodology | Demographic Factors | Population | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Contraceptive Agents | Contraception | Family Planning
Document Number: 330600

Peer Reviewed

Title: Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats.
Author: Misro MM; Chaki SP; Kaushik MC; Nandan D
Source: Contraception. 2009 Jun;79(6):488-97.
Abstract: BACKGROUND: The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive. STUDY DESIGN: Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals. RESULTS: Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter. CONCLUSION: Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.
Language: English
Keywords:
INDIA | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | MEN | INJECTABLES | TESTOSTERONE | ADMINISTRATION AND DOSAGE | STANDARDIZATION | REVERSIBLE STERILIZATION | MALE CONTRACEPTION | BODY WEIGHT | TIME FACTORS | SPERMICIDAL CONTRACEPTIVE AGENTS | Asia, Southern | Asia | Developing Countries | Research Methodology | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Androgens | Hormones | Endocrine System | Physiology | Biology | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Data Adjustment | Sterilization, Sexual | Population Dynamics | Contraceptive Agents
Document Number: 341101

6.
Title: Gene knockouts that affect male fertility: novel targets for contraception.
Author: Naz RK; Engle A; None R
Source: Frontiers In Bioscience. 2009;14:3994-4007.
Abstract: There is an urgent need for a better method of contraception that is accepted, effective, and available, due the population explosion and unintended pregnancy. Various targets are being investigated that can be used for contraception. The ideal target should be non-steroidal, intercourse-independent, non-surgical, reversible, and non-barrier with no side effects. The gene knockout technology is a powerful approach to identify such novel targets. We identified at least 93 genes whose deletion demonstrated an effect on fertility in male mice till 2004 (1). In the present article, we found 71 additional gene knockouts in the database since the last report which demonstrated an effect on male fertility. The majority of these knockouts also demonstrated an effect on non-reproductive organs concomitant with an anti-fertility effect or effect on other organs was not examined. The knockouts of only a few genes/proteins induced a specific effect on fertility without a serious side effect. These genes/proteins may provide novel targets for contraception/contraceptive vaccine development.
Language: English
Keywords:
WEST VIRGINIA | RESEARCH REPORT | CLINICAL RESEARCH | MEN | LABORATORY ANIMALS | GENETICS | REPRODUCTIVE BEHAVIOR | SEX BEHAVIOR | REVERSIBLE STERILIZATION | MALE STERILIZATION | CHROMOSOME ABNORMALITIES | PROTEINS | CONTRACEPTIVE VACCINES | Developed Countries | United States of America | North America | Americas | Research Methodology | Demographic Factors | Population | Biology | Fertility | Population Dynamics | Behavior | Sterilization, Sexual | Family Planning | Neonatal Diseases and Abnormalities | Diseases | Physiology | Contraception, Immunological | Contraception
Document Number: 330601

Peer Reviewed

Title: Status of contraceptive vaccines.
Author: Naz RK
Source: American Journal of Reproductive Immunology. 2009 Jan;61(1):11-8.
Abstract: PROBLEM: This is a review of anti-sperm contraceptive vaccines (CV), and synthesis of human scFv antibodies that can be used as immunocontraceptives. METHOD OF STUDY: Various methods of proteomics and genomics, peptide synthesis, phage display technology, and antibody engineering were used to obtain multi-epitope vaccines and human scFv antibodies from immunoinfertile and vasectomized men. The present review primarily focuses on the effect of multi-epitope vaccines and Izumo on fertility, and synthesis and characterization of sperm specific human scFv antibodies. RESULTS: The immunization with Izumo peptides causes a contraceptive effect in female mice. The efficacy is enhanced by combination vaccination, including peptides based on other sperm antigens. Using phage display technology, we were able to synthesize at least four novel scFv antibodies with unique complementarity determining regions (CDRs) that reacted with specific fertility-related sperm antigens. These antibodies inhibited human sperm function in vitro, and their immunocontraceptive effect in vivo by these antibodies is currently being investigated. CONCLUSION: The multi-epitope vaccines may provide an efficacious and viable approach to contraception. The human scFv antibodies, if they block fertility in vivo, may provide unique and novel immunocontraceptives, the first of its kind for human use. The multi-epitope CV and preformed engineered antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response.
Language: English
Keywords:
UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL RESEARCH | GENETIC TECHNIQUES | WOMEN | LABORATORY ANIMALS | CONTRACEPTIVE VACCINES | ANTIGENS | SPERMICIDAL CONTRACEPTIVE AGENTS | ANTIBODIES | GENETICS | CONTRACEPTIVE EFFECTIVENESS | Developed Countries | North America | Americas | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Demographic Factors | Population | Contraception, Immunological | Contraception | Family Planning | Immunologic Factors | Immunity | Immune System | Physiology | Biology | Contraceptive Agents
Document Number: 330063

Title: Novel Epididymal Proteins as Targets for the Development of Post-Testicular Male Contraception.
Author: Sipila P; Jalkanen J; Huhtaniemi IT; Poutanen M
Source: Reproduction. 2009;137:379-389.
Abstract: Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the postmeiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags (ESTs) in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genes in vivo. In this review we summarize the current knowledge of several epididymal proteins shown either in vivo or in vitro to be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52 and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.
Language: English
Keywords:
UNITED STATES OF AMERICA | LITERATURE REVIEW | GENETIC TECHNIQUES | CLINICAL RESEARCH | MEN | LABORATORY ANIMALS | MALE CONTRACEPTION | PROTEINS | SPERM MATURATION | GENETICS | EPIDIDYMIS | CONTRACEPTIVE AGENTS, MALE | Developed Countries | North America | Americas | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Research Methodology | Demographic Factors | Population | Contraception | Family Planning | Physiology | Biology | Spermatogenesis | Reproduction | Testis | Genitalia, Male | Genitalia | Urogenital System | Contraceptive Agents
Document Number: 329671

10.

Title: Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents.
Author: Dwivedy I; Gupta A; Grover A; Srivastava V; Singth MM
Source: Bioorganic and Medicinal Chemistry Letters. 2008;:[4] p.
Abstract: Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10),8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg-1. (author's)
Language: English
Keywords:
GLOBAL | CLINICAL RESEARCH | LABORATORY ANIMALS | ESTROGENS | CONTRACEPTION RESEARCH | IMPLANTATION | Research Methodology | Hormones | Endocrine System | Physiology | Biology | Contraception | Family Planning | Pregnancy, First Trimester | Pregnancy | Reproduction
Document Number: 327068

11.

Peer Reviewed

Title: Fetal and early postnatal environmental contaminant exposures and reproductive health effects in the female.
Author: Foster WG
Source: Fertility and Sterility. 2008 Feb;89(2 Suppl 1):e53-e54.
Abstract: The developing fetus and children are uniquely sensitive to the effects of biohazardous environmental toxicants that alter endocrine function. Exposure to environmental toxicants have been linked to developmental effects such as an increased prevalence of developmental abnormalities of the male reproductive tract. In young girls, advances in sexual development have been linked to exposure to phthalates, whereas others have been unable to demonstrate an effect of exposure to environmental toxicants and age at puberty. Although animal studies provide experimental evidence that supports the hypothesis that environmental toxicants can advance sexual development, little is known of the potential adverse health effects of exposure to environmental toxicants in the human female. Establishing a link between exposure to environmental toxicants and reproductive health effects in the female presents investigators with numerous daunting challenges. Among these challenges is the need to document exposure to environmental toxicants. (excerpt)
Language: English
Keywords:
CANADA | LITERATURE REVIEW | CLINICAL RESEARCH | FETUS | LABORATORY ANIMALS | PREGNANT WOMEN | ENVIRONMENT | REPRODUCTIVE HEALTH | POSTPARTUM | TOXICITY | CHROMOSOME ABNORMALITIES | RISK ASSESSMENT | North America, Northern | Americas | Developed Countries | Research Methodology | Pregnancy | Reproduction | Population Characteristics | Demographic Factors | Population | Health | Puerperium | Physiology | Biology | Neonatal Diseases and Abnormalities | Diseases | Evaluation
Document Number: 325259

12.

Peer Reviewed

Title: Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.
Author: Garc�a-Lerma JG; Otten RA; Qari SH; Jackson E; Cong Me
Source: PLoS Medicine. 2008 Feb;5(2):e28.
Abstract: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. Methods and Findings We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. Conclusions This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities. (author's)
Language: English
Keywords:
UNITED STATES OF AMERICA | GLOBAL | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | HIV PREVENTION | ANTIRETROVIRAL DRUGS | THEORETICAL MODELS | Developed Countries | North America | Americas | Research Methodology | HIV Infections | Viral Diseases | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health
Document Number: 324349

13.

Title: Progestin and breast cancer. The missing pieces of a puzzle.
Author: Giersig C
Source: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. 2008 Jul;51(7):782-6.
Abstract: The previous assumption that progestin does not promote breast cancer development needs to be re-examined since a growing body of evidence indicates the opposite. Data from recent experimental trials and results from clinical and epidemiological studies on hormonal contraceptives and hormone replacement therapy (HRT) have been confronted with breast cancer cases known from the German database of adverse drug reactions (ADR), reported in association with the use of progestin only contraceptives (POC) and combined oral contraceptives (COC). Also cases reported in association with HRT have been analysed. The available data complement one another showing a tumour promoting potential of progestin, possibly higher than that of a combination of estrogen and progestin. These assumptions are based on the following facts: 1) in estrogen-supplemented animals, progesterone has been shown to reactivate the growth of regressed tumour xenograft obtained from breast cancer cell lines, expressing both estrogen andprogesterone receptor; 2) antiprogestin has been revealed to suppress the reactivation of the growth of tumour xenograft and to fully suppress the development of breast cancer in an animal model for BRCA1 gene mutation; 3) metabolites of progesterone have been recognised as potent regulators of cell proliferation, cell detachment and apoptosis; 4) progesterone has been shown to inhibit, in a dose-dependent manner, apoptosis in breast cancer cell lines and apoptosis induced by doxorubicin and 5-fluorouracyl (drugs used in breast cancer treatment); 5) an association between breast cancer and HRT was suspected upon the addition of progestin on a regular basis for the prevention of endometrial cancer; 6) in a randomised placebo-controlled trial on HRT an increased risk of breast cancer was shown for the combination of estrogen and progestin, but not for estrogen alone; 7) in epidemiological studies on POC the recognition of an increased breast cancer risk was most probably impeded due to previously unrecognised systematic selection bias; 8) in a large epidemiological study on the risk of early-onset breast cancer in association with COC an increased risk was detected for COC use up to 1975, but no increased, even a slightly decreased, risk was shown for users of low-dose COC, applied since 1976; 9) a considerably higher number of breast cancer cases have been reported from Germany on POC than on the widespread used COC [corrected] (111 versus 12); 10) the big resemblance among the breast cancers reported for POC and their similarity with breast malignancies diagnosed in pregnancy suggest the existence of a pattern rather than pure coincidence [corrected]
Language: English
Keywords:
GLOBAL | SUMMARY REPORT | EPIDEMIOLOGY | CLINICAL RESEARCH | LABORATORY ANIMALS | HORMONE REPLACEMENT THERAPY | ESTROGENS | ORAL CONTRACEPTIVES, LOW-DOSE | BREAST CANCER | CONTRACEPTIVE AGENTS, PROGESTIN | Public Health | Health | Research Methodology | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Hormones | Endocrine System | Physiology | Biology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Contraceptive Agents, Female | Contraceptive Agents
Document Number: 328638

14.

Title: The inhibitory effects on adult male reproductive functions of crude garlic (Allium sativum) feeding.
Author: Hammami I; Nahdi A; Mauduit C; Benahmed M; Amri M
Source: Asian Journal of Andrology. 2008 Jul;10(4):593-601.
Abstract: Aim: To investigate the effects of crude garlic on adult male rat reproductive functions. Methods: Thirty male rats were divided into five groups: group 1 (untreated) and groups 2, 3, 4 and 5 were fed for 30 days with 5%, 10%, 15% and 30% crude garlic, respectively. Testes and accessory organs were weighed and some markers were assessed. Light and electron microscopy observations were also performed. Results: A significant decrease was observed in the body weight of groups 4 (14%; P < 0.01) and 5 (20%; P < 0.01); of the prostate weight in group 5 (29.1%; P < 0.05) and of seminal vesicle weight in groups 3 (14.4%; P < 0.01), 4 (18.3%; P < 0.01) and 5 (27.3%; P < 0.01). In contrast, testis and epididymis weights were unchanged. In epididymis tissue, the alpha glucosidase activity and the spermatozoa density were unchanged. The treatment resulted in a significant decrease in testosterone serum levels in groups 3 (77.3%; P < 0.01), 4 (77.3%; P < 0.01) and 5 (90.9%; P < 0.01), associated with a significant increase in LH serum levels (P < 0.01). Testicular histology showed a dose-dependent increase in the percentage of empty seminiferous tubules. Moreover, testicular function was affected; a significant decrease in phosphatase acid activity (P < 0.01) and testosterone (P < 0.05) contents were observed. Conclusion: Crude garlic consumption during 1 month reduced testosterone secretion and altered spermatogenesis at 10%, 15% and 30% doses. (author's)
Language: English
Keywords:
TUNISIA | RESEARCH REPORT | CASE CONTROL STUDIES | LABORATORY ANIMALS | MEN | MEDICINAL PLANTS | CONTRACEPTIVE AGENTS, MALE | BODY WEIGHT | PROSTATE | SPERMATOGENESIS BLOCKING AGENTS | TESTIS | ADMINISTRATION AND DOSAGE | TESTOSTERONE | LUTEINIZING HORMONE | Developing Countries | Africa, North | Africa | Studies | Research Methodology | Clinical Research | Demographic Factors | Population | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents | Contraception | Family Planning | Physiology | Biology | Genitalia, Male | Genitalia | Urogenital System | Drugs | Treatment | Medical Procedures | Androgens | Hormones | Endocrine System | Gonadotropins, Pituitary | Gonadotropins
Document Number: 327404

15.

Peer Reviewed

Title: Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection.
Author: Idh J; Westman A; Elias D; Moges F; Getachew A; Gelaw A; Sundqvist T; Forslund T; Alemu A; Ayele B; Diro E; Melese E; Wondmikun Y; Britton S; Stendahl O; Schon T
Source: BMC Infectious Diseases. 2008;8:146.
Abstract: BACKGROUND: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO). METHODS: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. RESULTS: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate. CONCLUSION: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.
Language: English
Keywords:
SWEDEN | RESEARCH REPORT | CROSS SECTIONAL ANALYSIS | CLIENTS | LABORATORY EXAMINATIONS AND DIAGNOSES | LABORATORY ANIMALS | TUBERCULOSIS | HIV INFECTIONS | TREATMENT | DRUGS | RISK FACTORS | Europe, Northern | Europe | Developed Countries | Research Methodology | Program Activities | Programs | Organization and Administration | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Clinical Research | Infections | Diseases | Viral Diseases | Biology
Document Number: 329356

16.

Peer Reviewed

Title: Evaluation of the potential of synthetic peptides of 80 kDa human sperm antigen (80 kDaHSA) for the development of contraceptive vaccine for male.
Author: Khobarekar BG; Vernekar V; Raghavan V; Kamada M; Maegawa M
Source: Vaccine. 2008 Jul 4;26(29-30):3711-3718.
Abstract: 80 kDaHSA has been demonstrated to be responsible for inducing immunoinfertility. Synthetic peptides NT, 1, 2 and 4 of 80 kDaHSA are immunogenic and immunobiologically mimic the native protein. Peptides 1 and NT being highly immunogenic their potential for contraceptive vaccine developmentwas evaluated. Active immunization of male rabbits with peptide-1 and -NT induced reversible infertility in 100% and 60% of animals, respectively and subsequently active immunization of non-human primate model, male marmosets with peptide-1 induced reversible infertility in six out of seven high antibody titer animals. The present study suggests the potential of peptide-1 of 80 kDaHSA for the development of contraceptive vaccine. (author's)
Language: English
Keywords:
GLOBAL | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | SPERMATOZOA | SPERM AGGLUTINATION | MALE CONTRACEPTION | CONTRACEPTIVE VACCINES | Research Methodology | Germ Cells | Genitalia | Urogenital System | Physiology | Biology | Antigen-Antibody Reactions | Antibodies | Immunologic Factors | Immunity | Immune System | Contraception | Family Planning | Contraception, Immunological
Document Number: 327042

17.

Peer Reviewed

Title: Chenopodium album seed extract-induced sperm cell death: Exploration of a plausible pathway.
Author: Kumar S; Chatterjee R; Dolai S; Adak S; Kabir SN
Source: Contraception. 2008 Jun;77(6):456-462.
Abstract: This study was conducted for to explore the plausible pathway of Chenopodium album seed extract (CAE)-mediated sperm cell death. The role of CAE for its spermicidal action was assessed by (a) measuring lipid peroxidation, protein carbonyl content and intracellular glutathione content in CAE exposed sperm cells; (b) assaying antioxidant enzymes like catalase and superoxide dismutase (SOD); (c) analyzing protein expressions by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis; (d) fluorimetric measurement of intracellular H2O2 level and generation of reactive oxygen species (ROS) in CAE-treated sperm cells; and (e) DNA ladder formation study. CAE-induced sperm death is due to (a) lipid peroxidation of the sperm cell membrane, oxidation of some critical cellular proteins and depletion of intracellular reduced gluthathione, indicating production of ROS; (b) activation of Mn-SOD and inactivation of catalase favoring endogenous accumulation of H2O2; (c) generationof O2 at an enhanced rate during oxidative stress as evidenced by increased Mn-SOD activity and protein expression; (d) accumulation of ROS in spermatozoa reflected in the fluorimetric experiments; and (e) increased production of O2 and H2O2 induced apoptosis-like death in sperm cells as observed by DNA ladder formation. The sperm death mediated by CAE is due to oxidative damage of cellular macromolecules by in situ generation of ROS. (author's)
Language: English
Keywords:
INDIA | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | CONTRACEPTION RESEARCH | SPERMATOGENESIS BLOCKING AGENTS | SPERMICIDAL CONTRACEPTIVE AGENTS | Developing Countries | Asia, Southern | Asia | Research Methodology | Contraception | Family Planning | Contraceptive Agents, Male | Contraceptive Agents
Document Number: 326729

18.

Title: Low levels of mammalian TGF-beta1 are protective against malaria parasite infection, a paradox clarified in the mosquito host.
Author: Luckhart S; Lieber MJ; Singh N; Zamora R; Vodovotz Y
Source: Experimental Parasitology. 2008 Feb;118(2):290-296.
Abstract: Nitric oxide (NO), derived from catalysis of inducible NO synthase (iNOS), limits malaria parasite growth in mammals. Transforming growth factor (TGF)-beta1 suppresses iNOS in cells in vitro as well as in vivo in mice, but paradoxically severe malaria in humans is associated with low levels of TGF-beta1. We hypothesized that this paradox is a universal feature of infection and occurs in the mosquito Anopheles stephensi, an invertebrate host for Plasmodium that also regulates parasite development with inducible NO synthase (AsNOS). We show that exogenous human TGF-beta1 dose-dependently regulates mosquito AsNOS expression and that parasite killing by low dose TGF-beta1 depends on AsNOS catalysis. Furthermore, induction of AsNOS expression by TGF-beta1 is regulated by NO synthesis. These results suggest that TGF-beta1 plays similar roles during parasite infection in mammals and mosquitoes and that this role is linked to the effects of TGF-beta1 on inducible NO synthesis. (author's)
Language: English
Keywords:
UNITED STATES OF AMERICA | RESEARCH REPORT | EVALUATION | LABORATORY ANIMALS | MALARIA | PARASITES | INSECTS | IMMUNOLOGIC FACTORS | IMMUNITY, CELLULAR | Developed Countries | North America | Americas | Clinical Research | Research Methodology | Parasitic Diseases | Diseases | Biology | Disease Transmission Control | Prevention and Control | Immunity | Immune System | Physiology
Document Number: 325604

19.

Title: Plasmodium berghei: Parasite clearance after treatment with dihydroartemisinin in an asplenic murine malaria model.
Author: Moore BR; Jago JD; Batty KT
Source: Experimental Parasitology. 2008 Apr;118(4):458-467.
Abstract: Clinical reports indicate that malaria-infected asplenic patients have a reduced capacity for parasite clearance despite intensive antimalarial therapy. The aim of this study was to evaluate the efficacy of dihydroartemisinin in an asplenic murine malaria model. Mice were inoculated with Plasmodium berghei parasitised erythrocytes and received a single dose of dihydroartemisinin 56 h later, at 2-5% parasitaemia. Haematology, liver biochemistry and histopathology of key organs were performed to evaluate organ response to malaria infection. The nadir parasitaemia occurred 20 h after dihydroartemisinin administration, falling 2.8- to 6.0-fold and 2.7- to 6.9-fold in asplenic and intact mice, respectively, (10-100 mg/kg). Histopathology indicated increased stimulation of liver function/activity during malaria infection of asplenic mice (as compared to intact mice). Overall efficacy of single-dose dihydroartemisinin treatment in asplenic mice was similar to intact mice although the rate of recrudescence in asplenic mice was significantly greater than intact mice at 30 and 100 mg/kg. The asplenic murine malaria model could be used in pre-clinical studies of splenic function and clearance of malaria parasites, pathophysiological studies or antimalarial drug efficacy in asplenia. (author's)
Language: English
Keywords:
DEVELOPING COUNTRIES | LITERATURE REVIEW | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | ANTIMALARIAL DRUGS | MALARIA PREVENTION | PARASITES | Research Methodology | Malaria | Parasitic Diseases | Diseases | Biology
Document Number: 325729

20.

Peer Reviewed

Title: Topical oestrogen keratinises the human foreskin and may help prevent HIV infection.
Author: Pask AJ; McInnes KJ; Webb DR; Short RV
Source: PLoS One. 2008 Jun;3(6):e2308.
Abstract: With the growing incidence of HIV, there is a desperate need to develop simple, cheap and effective new ways of preventing HIV infection. Male circumcision reduces the risk of infection by about 60%, probably because of the removal of the Langerhans cells which are abundant in the inner foreskin and are the primary route by which HIV enters the penis. Langerhans cells form a vital part of the body's natural defence against HIV and only cause infection when they are exposed to high levels of HIV virions. Rather than removing this natural defence mechanism by circumcision, it may be better to enhance it by thickening the layer of keratin overlying the Langerhans cells, thereby reducing the viral load to which they are exposed. We have investigated the ability of topically administered oestrogen to induce keratinization of the epithelium of the inner foreskin. Histochemically, the whole of the foreskin is richly supplied with oestrogen receptors. The epithelium of the inner foreskin, like the vagina,responds within 24 hours to the topical administration of oestriol by keratinization, and the response persists for at least 5 days after the cessation of the treatment. Oestriol, a cheap, readily available natural oestrogen metabolite, rapidly keratinizes the inner foreskin, the site of HIV entry into the penis. This thickening of the overlying protective layer of keratin should reduce the exposure of the underlying Langerhans cells to HIV virions. This simple treatment could become an adjunct or alternative to surgical circumcision for reducing the incidence of HIV infection in men. (author's)
Language: English
Keywords:
AUSTRALIA | RESEARCH REPORT | CLINICAL RESEARCH | MEN | LABORATORY ANIMALS | ESTROGENS | HIV PREVENTION | MALE CIRCUMCISION | HORMONE RECEPTORS | ESTRIOL | METABOLIC EFFECTS | Developed Countries | Oceania | Research Methodology | Demographic Factors | Population | Hormones | Endocrine System | Physiology | Biology | HIV Infections | Viral Diseases | Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Membrane Proteins
Document Number: 327417

21.

22.

Title: Gamma irradiated micro system for long-term parenteral contraception: An alternative to synthetic polymers.
Author: Puthli S; Vavia P
Source: European Journal of Pharmaceutical Sciences. 2008 Nov 15;35(4):307-17.
Abstract: An injectable system of levonorgestrel (LNG) was developed using biodegradable polymer of natural origin. The parenteral system was optimized for particle size and higher drug loading. The microparticulate system was characterised by scanning electron microscopy, encapsulation efficiency, moisture content, IR, DSC, XRD, residual solvent content, sterility testing, test of abnormal toxicity and test for pyrogens. The microparticles were sterilised by gamma irradiation (2.5Mrad). The system was injected intramuscularly in rabbits and the blood levels of LNG were determined using radioimmunoassay technique. An optimized drug to polymer ratio of 0.3-1.0 (w/w ratio) gave improved drug loading of about 52%. In vivo studies in rabbits showed that the drug was released in a sustained manner for a period of 1 month. The AUC(0-t) was found to be 9363.6+/-2340pg/mLday(-1) with MRT calculated to be about 16 days and Kel of 0.01day(-1). LNG levels were maintained between 200 and 400pg/mL. In vivo release exhibited an initial burst effect which was not observed in the in vitro dissolution. This promising "Progestin-only" long-term contraceptive with improved user compliance is an alternative to the synthetic expensive polymeric carriers.
Language: English
Keywords:
INDIA | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | WOMEN | INJECTABLES | LEVONORGESTREL | TOXICITY | ADMINISTRATION AND DOSAGE | TIME FACTORS | CONTRACEPTIVE EFFECTIVENESS | COST EFFECTIVENESS | Developing Countries | Asia, Southern | Asia | Research Methodology | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Physiology | Biology | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Population Dynamics | Evaluation Indexes | Quantitative Evaluation | Evaluation
Document Number: 330076

23.

Title: Spermicidal bacteriocins: Lacticin 3147 and subtilosin A.
Author: Silkin L; Hamza S; Kaufman S; Cobb SL; Vederas JC
Source: Bioorganic and Medicinal Chemistry Letters. 2008 May 15;18(10):3103-3106.
Abstract: Spermicidal compounds that also exhibit antimicrobial properties would be extremely attractive agents as they could be used to not only prevent unwanted pregnancy but also to combat the growing prevalence of sexually transmitted infections (STI). One class of compounds that are potential candidates for development of dual-acting contraceptive products are antimicrobial peptides (AMPs). Herein, we report preliminary studies carried out to investigate the spermicidal activity of two bacteriocins, lacticin 3147 and subtilosin A, on bovine, horse/pony, boar and rat sperm. (author's)
Language: English
Keywords:
GLOBAL | CLINICAL RESEARCH | LABORATORY ANIMALS | MICROBICIDES | CONTRACEPTION RESEARCH | SPERMICIDAL CONTRACEPTIVE AGENTS | SEXUALLY TRANSMITTED DISEASE PREVENTION | DUAL PROTECTION | Research Methodology | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraception | Family Planning | Contraceptive Agents | Sexually Transmitted Diseases | Reproductive Tract Infections | Infections | Diseases | Contraceptive Methods
Document Number: 327069

24.

Peer Reviewed

Title: Dynamics of acute and memory mucosal and systemic immune responses against HIV-1 envelope following immunizations through single or combinations of mucosal and systemic routes.
Author: Srivastava I; Goodsell A; Zhou F; Sun Y; Burke B
Source: Vaccine. 2008 May;26(22):2796-2806.
Abstract: In this study, immunizations at 2 weeks vs. 6 weeks intervals, with an HIV-1 envelope protein in adjuvants, through intra-nasal (IN), intra-muscular (IM), IN followed by IM (IN/IM) and IM/IN, were compared for induction of mucosal and systemic immune responses. IN/IM immunizations at 2, but not at 6, week intervals induced the highest mucosal and systemic immune responses compared to other immunization routes. Following a resting memory phase, IN boosting of IN/IM-immunized mice, compared to IM-boosting of IM-immunized mice, induced increased IgA responses. Thus, depending on the immunization intervals, IN/IM may be more effective than IM immunizations for short- and long-term immunity. (author's)
Language: English
Keywords:
UNITED STATES OF AMERICA | CALIFORNIA | RESEARCH REPORT | IMMUNIZATION SCHEDULE | VACCINES | LABORATORY ANIMALS | HIV PREVENTION | ANTIBODIES | ANTIBODY FORMATION | Developed Countries | North America | Americas | Immunization | Primary Health Care | Health Services | Delivery of Health Care | Health | Medical Procedures | Medicine | Clinical Research | Research Methodology | HIV Infections | Viral Diseases | Diseases | Immunologic Factors | Immunity | Immune System | Physiology | Biology
Document Number: 326741

25.

Peer Reviewed

Title: Surfactants as microbicides and contraceptive agents: a systematic in vitro study.
Author: Vieira OV; Hartmann DO; Cardoso CM; Oberdoerfer D; Baptista M; Santos MA; Almeida L; Ramalho-Santos J; Vaz WL
Source: PLoS One. 2008;3(8):e2913.
Abstract: BACKGROUND: The urgent need for cheap and easy-to-use protection against both unwanted pregnancies and sexually transmitted diseases has stimulated considerable interest in the use of surfactants as microbicides, anti-viral, and contraceptive agents in recent years. In the present study we report a systematic in vitro evaluation of the microbicidal, anti-viral and contraceptive potential of cationic, anionic, zwitterionic, and non-ionic surfactants. METHODOLOGY/PRINCIPAL FINDINGS: Toxicity was evaluated in mammalian columnar epithelial (MDCK) cells, human sperm cells, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Streptococcus agalactiae and Enterococcus faecalis. The inhibition of adenovirus and lentivirus infection of MDCK cells was also tested. A homologous series of cationic surfactants, alkyl-N,N,N-trimethylammonium bromides (C(n)TAB), with varying alkyl chains were shown to be bactericidal and fungicidal at doses that were related to the surfactant critical micelle concentrations (CMC), all of them at concentrations significantly below the CMC. In general, bacteria were more susceptible to this surfactant group than C. albicans and this organism, in turn, was more susceptible than MDCK cells. This suggests that the C(n)TAB may be useful as vaginal disinfectants only in so far as bacterial and fungal infections are concerned. None of the surfactants examined, including those that have been used in pre-clinical studies, showed inhibition of adenovirus or lentivirus infection of MDCK cells or spermicidal activity at doses that were sub-toxic to MDCK cells. CONCLUSIONS/SIGNIFICANCE: The results of this study lead us to propose that systematic analysis of surfactant toxicity, such as we report in the present work, be made a mandatory pre-condition for the use of these substances in pre-clinical animal and/or human studies.
Language: English
Keywords:
PORTUGAL | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN | LABORATORY ANIMALS | IN VITRO | MICROBICIDES | VAGINAL GEL | SEXUALLY TRANSMITTED DISEASE PREVENTION | VAGINAL FOAM | BACTERIAL AND FUNGAL DISEASES | ANTIVIRAL DRUGS | Europe, Southwestern | Europe | Developed Countries | Research Methodology | Demographic Factors | Population | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Vaginal Spermicides | Contraceptive Methods | Contraception | Family Planning | Sexually Transmitted Diseases | Reproductive Tract Infections | Infections | Diseases
Document Number: 329236

26.

Title: Comparative effects of oral conjugated equine estrogens and micronized 17beta-estradiol on breast proliferation: a retrospective analysis.
Author: Wood CE; Clarkson TB; Chen H; Veenstra TD; Xu X; Scott L; Cline JM
Source: Menopause. 2008 Sep-Oct;15(5):890-8.
Abstract: OBJECTIVE: To evaluate the effects of oral conjugated equine estrogens (CEE) and micronized 17beta-estradiol (E2) on breast proliferation in a postmenopausal primate model. DESIGN: Data from nine studies were analyzed retrospectively. The primary outcome measure was breast epithelial proliferation determined by immunolabeling for the Ki67 antigen. Other measures included progesterone receptor expression and endometrial thickness (as surrogate markers of systemic estrogen exposure) and urinary estrogen metabolite profile. All CEE doses were given at the human equivalent of 0.625 mg/day (n = 281), whereas E2 was given at the human equivalent of 1.0 mg/day or less (n = 131). RESULTS: Oral CEE resulted in a modest overall increase in breast epithelial proliferation of 75% that reached significance at P < 0.05 compared with placebo in one of four parallel-arm studies. In contrast, oral E2 resulted in a more substantial increase in breast epithelial proliferation of 259% (all studies) to 330% (parallel-arm studies only) that reached significance at P < 0.05 in all five E2 studies evaluated. Breast epithelial expression of progesterone receptor, a widely used marker of estrogen receptor activity, and endometrial thickness showed similar increases after treatment with CEE and E2 (P < 0.05 in all available studies). Relative amounts of urinary methoxyestrogens and the 2-hydroxyestrogen-to-16alpha-hydroxyestrone ratio were higher after CEE compared with E2 treatment (P < 0.05 for all). CONCLUSIONS: This retrospective analysis of oral estrogen effects in postmenopausal macaques suggests that standard doses of CEE may result in less estrogen-induced epithelial proliferation in the breast compared with E2.
Language: English
Keywords:
UNITED STATES OF AMERICA | RESEARCH REPORT | LITERATURE REVIEW | CLINICAL RESEARCH | LABORATORY ANIMALS | WOMEN | ESTROGENS | ESTRADIOL | ORAL CONTRACEPTIVES | MENOPAUSE | ANTIGENS | PROGESTERONE | BREAST CANCER | SIDE EFFECTS | HORMONE REPLACEMENT THERAPY | Developed Countries | North America | Americas | Research Methodology | Demographic Factors | Population | Hormones | Endocrine System | Physiology | Biology | Contraceptive Methods | Contraception | Family Planning | Reproduction | Immunologic Factors | Immunity | Immune System | Progestational Hormones | Cancer | Neoplasms | Diseases | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health
Document Number: 329630

27.
Title: Combined estrogen-progestogen contraceptives and combined estrogen-progestogen menopausal therapy.
Author: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans
Source: IARC Monographs On the Evaluation of Carcinogenic Risks to Humans. 2007;91:1-528.
Abstract: In June, 2005, 21 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to assess the carcinogenicity of combined (oestrogen-progestagen) contraceptives and hormone therapy to humans.
Language: English
Keywords:
GLOBAL | LITERATURE REVIEW | DATA STORAGE AND RETRIEVAL | RISK ASSESSMENT | INCIDENCE | LABORATORY ANIMALS | CANCER | EXPOSURE | INORGANIC CHEMICALS | NEOPLASMS | TESTING | Information Processing | Information | Evaluation | Measurement | Research Methodology | Clinical Research | Diseases | Risk Factors | Biology | Ingredients and Chemicals
Document Number: 328696

28.
Peer Reviewed

Title: Miglustat has no apparent effect on spermatogenesis in normal men.
Author: Amory JK; Muller CH; Page ST; Leifke E; Pagel ER
Source: Human Reproduction. 2007 Mar;22(3):702-707.
Abstract: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertilty, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control. (author's)
Language: English
Keywords:
WASHINGTON | RESEARCH REPORT | PILOT PROJECTS | CLINICAL RESEARCH | MEN | LABORATORY ANIMALS | SPERMATOGENESIS BLOCKING AGENTS | ADMINISTRATION AND DOSAGE | SPERM COUNT | SPERMATOZOA | SIDE EFFECTS | BODY WEIGHT | DIARRHEA | LIPIDS | ENZYME INHIBITORS | United States of America | North America | Americas | Developed Countries | Studies | Research Methodology | Demographic Factors | Population | Contraceptive Agents, Male | Contraceptive Agents | Contraception | Family Planning | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Germ Cells | Genitalia | Urogenital System | Physiology | Biology | Diseases | Enzymes and Enzyme Inhibitors
Document Number: 312204

29.

Title: Postnatal development and reproductive performance of F1 progeny exposed in utero to ayurvedic contraceptive: Pippaliyadi yoga.
Author: Balasinor N; Bhan A; Paradkar NS; Shaikh A; Nandedkar TD
Source: Journal of Ethnopharmacology. 2007 Feb;109(3):406-411.
Abstract: Pippaliyadi yoga or pippaliyadi vati is an ayurvedic contraceptive used in India since ancient times. It is a combination of powdered fruit berries of Embelia ribes Burm.f. (Myrsinaceae), Piper longum L. (Piperaceae) and borax in equal proportion. Though the contraceptive potential is known since ancient times, no systematic developmental toxicity studies have been carried out. The present study was carried out to evaluate the postnatal developmental toxicity and the reproductive performance of the progeny exposed in utero to pippaliyadi. Pippaliyadi yoga was obtained from National Institute for Pharmaceutical Education and Research (NIPER), India and the developmental toxicity was studied by administering three doses, viz. 140, 300 and 700 mg/(kg day) to gravid females from day 6 to day 16 of gestation. Pippaliyadi did not have any adverse developmental effects with low doses, however, with the five times higher dose, a decrease in body weight of the pups was observed. The reproductive performance of the progeny born to mothers treated with pippaliyadi was not significantly affected. The present study suggests that in utero exposure to pippaliyadi does not have any adverse effect on the postnatal development and reproductive performance of the F/1 progeny. (author's)
Language: English
Keywords:
INDIA | RESEARCH REPORT | CLINICAL RESEARCH | LABORATORY ANIMALS | TOXICITY | TRADITIONAL MEDICINE | MEDICINAL PLANTS | REPRODUCTION | GROWTH | CONTRACEPTION | Asia, Southern | Asia | Developing Countries | Research Methodology | Physiology | Biology | Medicine | Health Services | Delivery of Health Care | Health | Child Development | Family Planning
Document Number: 314467

30.
Title: Recent evidence from human and animal studies regarding iron status and infant development.
Author: Beard J
Source: Journal of Nutrition. 2007 Feb;137(2):524S-530S.
Abstract: Infants are at risk for iron deficiency as breast milk or formula is replaced by semisolid foods during weaning. The scope of this article is to briefly review new findings on developmental iron deficiency and the persistence of deficiency effects into adulthood. A lack of sufficient iron intake may significantly delay the development of the central nervous system because of alterations in morphology, neurochemistry, and bioenergics. Depending on the stage of development at the time of iron deficiency, there may be an opportunity to reverse adverse effects, but the success of repletion efforts may be time dependent. The program project on ''Brain and Behavior in Early Iron Deficiency'' (B. Lozoff, P.I.) undertook preclinical and clinical studies to identify the regions of the brain and behaviors affected, and perhaps irreversibly altered, by early-life iron deficiency. Multiple outcomes are being measured in humans, nonhuman primates, and rodents. Data in monkeys show significant effects on neurodevelopment with dietary iron deficiency. Findings in human infants are consistent with altered myelination and changes in monoamine functioning. Rodent studies show that effects of iron deficiency during gestation and lactation persist despite restoration of iron status at weaning. These cross-species studies indicate a vulnerable period in early development that may result in long-lasting damage. (author's)
Language: English
Keywords:
DEVELOPING COUNTRIES | LITERATURE REVIEW | CLINICAL RESEARCH | INFANT | LABORATORY ANIMALS | HEALTH SURVEYS | EPIDEMIOLOGIC METHODS | CHILD DEVELOPMENT | SERUM IRON LEVEL | ANEMIA | DEFICIENCY DISEASES | CENTRAL NERVOUS SYSTEM EFFECTS | Research Methodology | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Health | Biology | Hemic System | Physiology | Diseases | Nutrition Disorders | Central Nervous System
Document Number: 312509


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