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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 -
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 -
Public Health Jun 2023This study aimed to (1) provide a comprehensive overview of contraceptive methods self-reported by men in England, over 5 years, focusing on condoms in comparison to any... (Review)
Review
A comprehensive overview by region of condoms, natural family planning, and spermicide as a contraceptive method among men aged 13-54 years attending contraceptive services in England.
OBJECTIVES
This study aimed to (1) provide a comprehensive overview of contraceptive methods self-reported by men in England, over 5 years, focusing on condoms in comparison to any male method; and (2) explore condom as a contraceptive method by region and ethnicity.
STUDY DESIGN
Data were from the Sexual and Reproductive Health Services (Contraception) England census data set from 2014/15 to 2018/19. Once missing data were removed, this left a total of 365,292 men. Two binomial logistic regression models were performed. Model 1 examined ethnicity, region, and time on condom as a method of contraception; and Model 2 examined ethnicity, region, and time by any male contraceptive. Descriptive statistics were run for natural family planning and spermicide.
RESULTS
Model 1 revealed a significant model, χ (15) = 30,976, P < 0.001, and predicted that condoms as a method decreased in London with a greater decrease in Midlands. London saw the lowest rate of decline among the non-White ethnic group, whereas North and South regions increased probability over time. The North started at a higher probability and the South at the lowest. Model 2 also revealed a significant model, χ (15) = 32,472, P < 0.001, with a similar pattern to Model 1. Contingency tables showed natural family planning and spermicide were the least reported methods and decreased over time.
CONCLUSIONS
As any male contraceptive method appears to be decreasing in both models, reproductive health promotion is required. This study has implications for commissioning funds and for identifying regional areas of further investigation.
Topics: Female; Male; Humans; Condoms; Contraceptive Agents; Natural Family Planning Methods; Contraception; Spermatocidal Agents
PubMed: 37163786
DOI: 10.1016/j.puhe.2023.03.023 -
Reproduction & Fertility Jan 2022To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions.
METHODS
A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well.
RESULTS
In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies.
CONCLUSIONS
N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies.
LAY SUMMARY
Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.
Topics: Female; Humans; Male; Nonoxynol; Semen; Sperm Motility; Spermatocidal Agents; Spermatozoa
PubMed: 35350652
DOI: 10.1530/RAF-21-0024 -
The Cochrane Database of Systematic... 2001The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have... (Review)
Review
BACKGROUND
The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have advocated alternative guidelines for the use of diaphragms.
OBJECTIVES
The objective of this review was to compare the effectiveness, safety and acceptability of the diaphragm with and without spermicide.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, POPLINE, CINAHL, the Cochrane Controlled Trials Register, and reference lists of relevant articles. In addition, we contacted experts in the field to identify unpublished studies.
SELECTION CRITERIA
Randomized controlled trials comparing women of reproductive age using the diaphragm with and without spermicide as the sole contraceptive method that reported clinical outcomes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data on outcomes and trial characteristics and any discrepancies were resolved by consensus or by consultation with the third reviewer. The results of the one identified study are presented descriptively.
MAIN RESULTS
We identified only one study. No significant difference was found in the pregnancy rates (with typical use or consistent use) or discontinuation rates between the diaphragm-with-spermicide and diaphragm-without-spermicide groups. There was a trend towards higher pregnancy rates in the diaphragm-without-spermicide group. However, this study failed to recruit the planned number of participants and was consequently underpowered.
REVIEWER'S CONCLUSIONS
As only one underpowered study was identified, we cannot distinguish between the contraceptive effectiveness of the diaphragm with and without spermicide. We cannot draw any conclusion at this point, further research is needed.
Topics: Contraception; Contraceptive Devices, Female; Female; Humans; Pregnancy; Randomized Controlled Trials as Topic; Spermatocidal Agents
PubMed: 11406025
DOI: 10.1002/14651858.CD002031 -
Pharmaceuticals (Basel, Switzerland) Mar 2016The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for... (Review)
Review
The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women's body. For this reason, antimicrobial peptides (AMPs), naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI.
PubMed: 26978373
DOI: 10.3390/ph9010013 -
Journal of Biomedicine & Biotechnology 2009Sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), the causative agents of acquired immunodeficiency syndrome (AIDS), are two great concerns... (Review)
Review
Sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), the causative agents of acquired immunodeficiency syndrome (AIDS), are two great concerns in the reproductive health of women. Thus, the challenge is to find products with a double activity, on the one hand having antimicrobial/antiviral properties with a role in the reduction of STI, and on the other hand having spermicidal action to be used as a contraceptive. In the absence of an effective microbicide along with the disadvantages of the most commonly used spermicidal contraceptive worldwide, nonoxynol-9, new emphasis has been focused on the development of more potential intravaginal microbicidal agents. Topical microbicides spermicides would ideally provide a female-controlled method of self-protection against HIV as well as preventing pregnancies. Nonoxynol-9, the only recommended microbicide spermicide, damages cervicovaginal epithelium because of its membrane-disruptive properties. Clearly, there is an urgent need to identify new compounds with dual potential microbicidal properties; antimicrobial peptides should be candidates for such investigations. Dermaseptins and magainins are two classes of cationic, amphipathic alpha-helical peptides that have been identified in the skin extracts of frogs Phyllomedusa sauvagei and Xenopus laevis. Regarding their contraceptive activities and their effect against various STI-causing pathogens, we believe that these two peptides are appropriate candidates in the evaluation of newer and safer microbicides spermicides in the future.
Topics: Amphibian Proteins; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Female; Humans; Magainins; Male; Ranidae; Sexually Transmitted Diseases; Skin; Spermatocidal Agents
PubMed: 19893636
DOI: 10.1155/2009/452567 -
Biomedicine & Pharmacotherapy =... Jun 2020dl-Mandelic acid (MA), an alpha-hydroxycarboxylic acid, has been widely used as an intermediate of pharmaceutical and fine chemicals. Here, we evaluated the... (Review)
Review
dl-Mandelic acid (MA), an alpha-hydroxycarboxylic acid, has been widely used as an intermediate of pharmaceutical and fine chemicals. Here, we evaluated the sperm-immobilizing activity of MA and its safety profiles. Spermatozoon motility was assessed by computer-aided sperm analysis, the integrity of the plasma membrane and. mitochondrial potential was assessed using fluorescein isothiocyanate-pisum sativum agglutinin and JC-1, respectively. The local tolerance of the MA-containing gel formulation was evaluated using a rabbit vaginal irritation test. We found that MA inhibited sperm motility and movement patterns in a concentration-dependent manner. Within 20 s, MA-induced spermatozoa immobilization occurred with a minimum effective concentration and a median effective concentration of 0.86 and 0.54 mg/mL, respectively. Plasma membrane disruptions of MA-treated spermatozoa were relatively mild, but mitochondrial depolarization occurred. Histopathological examination showed that MA exposure did not exert obvious effects on the integrity of spermatozoa membrane structures and only caused slight irritation to the rabbit vaginal epithelium. The vaginal irritation scores of the vehicle control and the nonoxynol -9 gel control groups were 1.38 ± 0.65 and 7.88 ± 1.67, respectively (p < 0.01), whereas those of the MA gel groups at 10, 20, and 40 mg/mL were 1.69 ± 1.04, 2.98 ± 0.77, and 4.35 ± 1.04 with p values of >0.05, >0.05, and <0.05 (vs. vehicle control), respectively, which were within the clinically acceptable range (<8). Therefore, our results confirmed that MA exhibited significant sperm-immobilizing effects and caused mild plasma membrane injury, suggesting that it has potential for development as a future non-surfactant spermicide.
Topics: Animals; Cell Proliferation; Contraception; Dose-Response Relationship, Drug; Female; Humans; Male; Mandelic Acids; Membrane Potential, Mitochondrial; Mucous Membrane; Rabbits; Sperm Motility; Spermatocidal Agents; Spermatozoa; Vagina
PubMed: 32224371
DOI: 10.1016/j.biopha.2020.110104 -
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