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Fertility and Sterility Jun 2021Despite significant interests in contraception by men, effective methods of male contraception are limited to vasectomy and condoms. Recently, there have been several... (Review)
Review
Despite significant interests in contraception by men, effective methods of male contraception are limited to vasectomy and condoms. Recently, there have been several promising advances in male contraceptive research. This review will update readers on recent research in both hormonal and nonhormonal approaches to male contraception. Hormonal approaches to male contraception have been stymied by adverse effects, formulations requiring injections or implants, a 5% to10% nonresponse rate, as well as poor understanding of user acceptability. In the last several years, research has focused on novel, orally bioavailable androgens such as dimethandrolone undecanoate and 11β-methyl-19-nor-testosterone. Additionally, combinations of a topical testosterone gel combined with a gel containing segesterone acetate, a potent progestin, have shown promise in clinical trials recently. Simultaneously, significant preclinical progress has been made in several approaches to nonhormonal male contraceptives, including compounds that inhibit sperm motility such as eppin, compounds that inhibit retinoic acid binding or biosynthesis, and reversible approaches to obstruction of the vas deferens. It is imperative for these areas of research to continue making strides so that there is a gamut of contraceptive options for couples to choose from. Some of these approaches will hopefully reach clinical utility soon, greatly improving contraceptive choice for couples.
Topics: Animals; Antispermatogenic Agents; Contraceptive Agents, Hormonal; Contraceptive Effectiveness; Female; Fertility; Humans; Male; Men's Health; Pregnancy; Pregnancy, Unplanned; Pregnancy, Unwanted; Spermatogenesis; Treatment Outcome
PubMed: 33931201
DOI: 10.1016/j.fertnstert.2021.03.047 -
Journal of Pharmacy & Pharmaceutical... 2007Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often... (Review)
Review
PURPOSE
Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often complicate study of the biological effects of the main ingredient. The presence of small amounts of endotoxin in recombinant protein preparations can cause side effects in host organism such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove endotoxins from drugs, injectables, and other biological and pharmaceutical products. An overview of this subject is provided by this article.
METHODS
An extensive review of literature with regard to methods for removal of endotoxin from biotechnological preparations was carried out.
RESULTS
A short history of endotoxin is presented first. This is followed by a review of chemical and physical properties of endotoxin and its pathophysiological effects when the body is exposed to LPS excessively or systemically. The techniques of endotoxin determination and interaction of endotoxin with proteins is also presented, taking into consideration the established techniques as well as the state of the art technology in this field. A review of techniques of endotoxin removal from biotechnological preparations is described, emphasizing how endotoxin removal can be carried out in an economical way based on a number of processes discussed in the literature (e.g., adsorption, two-phase partitioning, ultrafiltration and chromatography). Different methods are mentioned with relatively high protein recoveries; however, special attention is given to two-phase aqueous micellar systems, which are valuable tools for endotoxin removal from pharmaceutical proteins on a small scale because they provide a mild environment for biological materials.
CONCLUSIONS
Efficient and cost-effective removal of endotoxins from pharmaceutical and biotechnology preparations is challenging. Despite development of novel methods, such as the two-phase aqueous micellar systems, in recent years, more research is needed in this field.
Topics: Biological Products; Chromatography, Liquid; Cost-Benefit Analysis; Drug Contamination; Endotoxins; History, 19th Century; History, 20th Century; Micelles; Octoxynol; Polyethylene Glycols; Quality Control; Ultrafiltration
PubMed: 17727802
DOI: No ID Found -
Best Practice & Research. Clinical... Aug 2014Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on... (Review)
Review
Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the non-hormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed.
Topics: Adamantane; Administration, Cutaneous; Androgens; Animals; Antispermatogenic Agents; Azoospermia; Clinical Trials as Topic; Contraception; Contraceptive Agents, Male; Contraceptives, Oral, Synthetic; Desogestrel; Drug Implants; Estrenes; Evidence-Based Medicine; Gels; Humans; Injections, Intramuscular; Levonorgestrel; Male; Oligospermia; Progestins; Sperm Count; Testosterone; Vasectomy
PubMed: 24947599
DOI: 10.1016/j.bpobgyn.2014.05.008 -
Journal of the Chinese Medical... Jul 2015The aim of this review was to provide a comprehensive summary of medicinal plants used as antifertility agents in females throughout the world by various tribes and... (Review)
Review
The aim of this review was to provide a comprehensive summary of medicinal plants used as antifertility agents in females throughout the world by various tribes and ethnic groups. We undertook an extensive bibliographic review by analyzing classical text books and peer reviewed papers, and further consulting well accepted worldwide scientific databases. We performed CENTRAL, Embase, and PubMed searches using terms such as "antifertility", "anti-implantation", "antiovulation", and "antispermatogenic" activity of plants. Plants, including their parts and extracts, that have traditionally been used to facilitate antifertility have been considered as antifertility agents. In this paper, various medicinal plants have been reviewed for thorough studies such as Polygonum hydropiper Linn, Citrus limonum, Piper nigrum Linn, Juniperis communis, Achyanthes aspera, Azadirachta indica, Tinospora cordifolia, and Barleria prionitis. Many of these medicinal plants appear to act through an antizygotic mechanism. This review clearly demonstrates that it is time to expand upon experimental studies to source new potential chemical constituents from medicinal plants; plant extracts and their active constituents should be further investigated for their mechanisms. This review creates a solid foundation upon which to further study the efficacy of plants that are both currently used by women as traditional antifertility medicines, but also could be efficacious as an antifertility agent with additional research and study.
Topics: Abortifacient Agents; Animals; Embryo Implantation; Female; Fertility; Humans; Ovulation; Plant Extracts; Plants, Medicinal; Spermatogenesis
PubMed: 25921562
DOI: 10.1016/j.jcma.2015.03.008 -
Biochimica Et Biophysica Acta Dec 2016Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and... (Review)
Review
Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and photodynamic-therapy and hyperthermia. Although the mechanism of action remained unclear, LND treatment has been known to target metabolic pathways in cancer cells. It has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibited l-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Recent studies have demonstrated that LND potently inhibits MPC activity in isolated rat liver mitochondria (K 2.5μM) and cooperatively inhibits l-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K and Hill coefficient values of 36-40μM and 1.65-1.85, respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC~7μM) than other substrates including glutamate (IC~20μM). LND inhibits the succinate-ubiquinone reductase activity of respiratory Complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through Complex II and has been reported to promote cell death by suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated l-lactic acid efflux, Complex II and glutamine/glutamate oxidation.
Topics: Animals; Antineoplastic Agents; Hexokinase; Humans; Hydrogen-Ion Concentration; Indazoles; Membrane Transport Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Monocarboxylic Acid Transporters; Pyruvic Acid
PubMed: 27497601
DOI: 10.1016/j.bbcan.2016.08.001 -
Antimicrobial Agents and Chemotherapy Sep 2011Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used...
Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro. Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas. We report here the in vitro activities, structure-activity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro, the new compounds appeared to be safer than N-9 for vaginal use.
Topics: Antiprotozoal Agents; Female; HeLa Cells; Humans; In Vitro Techniques; Male; Metronidazole; Spermatocidal Agents; Spermatozoa; Structure-Activity Relationship; Trichomonas vaginalis
PubMed: 21709091
DOI: 10.1128/AAC.00199-11 -
American Family Physician Jan 2004When used with a spermicide, the diaphragm can be a more effective barrier contraceptive than the male condom. The diaphragm allows female-controlled contraception. It... (Review)
Review
When used with a spermicide, the diaphragm can be a more effective barrier contraceptive than the male condom. The diaphragm allows female-controlled contraception. It also provides moderate protection against sexually transmitted diseases and is less expensive than some contraceptive methods (e.g., oral contraceptive pills). However, diaphragm use is associated with more frequent urinary tract infections. Contraindications to use of a diaphragm include known hypersensitivity to latex (unless the wide seal rim diaphragm is used) or a history of toxic shock syndrome. A diaphragm is fitted properly if the posterior rim rests comfortably in the posterior fornix, the anterior rim rests snugly behind the pubic bone, and the cervix can be felt through the dome of the device. The diaphragm should not be left in the vagina for longer than 24 hours. When the diaphragm is the chosen method of contraception, patient education is key to compliance and effectiveness. An extended visit with the physician or a nurse may be required for a woman to learn proper insertion, removal, and care of the diaphragm.
Topics: Anthropometry; Cervix Uteri; Contraception; Contraceptive Devices, Female; Contraindications; Equipment Design; Female; Humans; Latex Hypersensitivity; Palpation; Patient Compliance; Patient Education as Topic; Shock, Septic; Spermatocidal Agents; Time Factors; Urinary Tract Infections; Vagina
PubMed: 14727824
DOI: No ID Found -
Indian Journal of Cancer 2014Garlic is one of the components, which have effects on reducing the risk of cancer. Including garlic in the diet helps for the betterment of the health. Medicinal... (Review)
Review
Garlic is one of the components, which have effects on reducing the risk of cancer. Including garlic in the diet helps for the betterment of the health. Medicinal effects of the garlic were known since 5,000 years. Recently, studies were carried out to known its effect on the cancer cell lines. Many studies have shown its effects not only on carcinomas, but also on the cardiovascular system and immune system. Functions of the each component of the garlic were studied to know exactly, which component has got beneficial effect. So this review has been carried out to know about the component, functions of each component, mode of action, and beneficial effects of the garlic.
Topics: Allyl Compounds; Animals; Chemoprevention; Cysteine; Diet; Dipeptides; Disulfides; Garlic; Humans; Immune System; Immunomodulation; Neoplasms; Phytotherapy; Plant Preparations; Protective Factors; Sulfides
PubMed: 26842201
DOI: 10.4103/0019-509X.175383 -
Therapeutic Advances in Reproductive... 2023Access to reliable contraception is a pillar of modern society. The burden of unintended pregnancy has fallen disproportionately on the mother throughout human history;... (Review)
Review
Access to reliable contraception is a pillar of modern society. The burden of unintended pregnancy has fallen disproportionately on the mother throughout human history; however, recent legal developments surrounding abortion have sparked a renewed interest in male factor contraceptives beyond surgical sterilization and condoms. Modern efforts to develop reversible male birth control date back nearly a century and initially focused on altering the hypothalamic-pituitary-testes axis. These hormonal contraceptives faced multiple barriers, including systemic side effects, challenging dosing regimens, unfavorable routes of delivery, and the public stigma surrounding steroid use. Novel hormonal agents are seeking to overcome these barriers by limiting the side effects and simplifying use. Non-hormonal contraceptives are agents that target various stages of spermatogenesis; such as inhibitors of retinoic acid, Sertoli cell-germ cell interactions, sperm ion channels, and other small molecular targets. The identification of reproductive tract-specific genes associated with male infertility has led to more targeted drug development, made possible by advances in CRISPR and proteolysis targeting chimeras (PROTACs). Despite multiple human trials, no male birth control agents have garnered regulatory approval in the United States or abroad. This narrative review examines current and emerging male contraceptives, including hormonal and non-hormonal agents.
PubMed: 36909934
DOI: 10.1177/26334941221138323 -
Asian Journal of Andrology 2018The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that... (Review)
Review
The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.
Topics: Age Factors; Androgens; Antispermatogenic Agents; Cardiovascular Diseases; Contraceptive Agents, Male; Gonadotropins; Humans; Male; Progestins; Testosterone
PubMed: 29384141
DOI: 10.4103/aja.aja_2_18