17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, is an effective spermicide and microbicide against Neisseria gonorrhoeae.

STUDY QUESTION: Is 17BIPHE2, an engineered cathelicidin antimicrobial peptide with low susceptibility to proteases, a better spermicide in cervicovaginal fluid (CVF) than its parental peptides, LL-37 and GF-17? SUMMARY ANSWER: At the same mass concentration, 17BIPHE2 exhibited the highest spermicidal activity on human sperm resuspended in CVF-containing medium. WHAT IS KNOWN ALREADY: LL-37 and its truncated peptide GF-17 exert both spermicidal and microbicidal activities, although they are prone to proteolytic degradation in body fluids. STUDY DESIGN, SIZE, DURATION: Spermicidal activities of 17BIPHE2 were evaluated in vitro in mouse and human sperm, both resuspended in medium, and then on human sperm incubated in CVF-containing medium; in the latter condition, the spermicidal activity and peptide stability in CVF of 17BIPHE2 were compared with that of LL-37 and GF-17. The in vivo contraceptive effects of 17BIPHE2 and the reversibility thereof were then assessed in mice. Finally, in vitro microbicidal effects of 17BIPHE2 on Neisseria gonorrhoeae were determined. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm motility and plasma membrane integrity were assessed by videomicroscopy and exclusion of Sytox Green, a membrane-impermeable fluorescent dye, respectively. Successful in vitro fertilization (IVF) was determined by the presence of two pronuclei in oocytes following their coincubation with capacitated untreated or 17BIPHE2-treated sperm. Sperm alone or with 17BIPHE2 were transcervically injected into female mice and successful in vivo fertilization was indicated by the formation of two-cell embryos 42-h postinjection, and by pregnancy through pup delivery 21-25 days afterwards. Peptide intactness was assessed by immunoblotting and HPLC. Reversibility of the contraceptive effects of 17BIPHE2 was evaluated by resumption of pregnancy of the female mice, pretranscervically injected with 17BIPHE2, following natural mating with fertile males. Minimum inhibitory/bactericidal concentrations of 17BIPHE2 on N. gonorrhoeae were obtained through microdilution broth assay. MAIN RESULTS AND THE ROLE OF CHANCE: At the same mass concentration, 17BIPHE2 was a more effective spermicide than LL-37 or GF-17 on human sperm resuspended in CVF-containing medium, with the spermicidal concentration of 32.4 µM. This was mainly due to lower susceptibility of 17BIPHE2 to CVF proteases. Importantly, the reproductive tract of mouse females treated three times with 32.4 µM 17BIPHE2 remained normal and their fecundity resumed after stopping 17BIPHE2 treatment. LIMITATIONS, REASONS FOR CAUTION: For ethical reasons, the inhibitory effects of 17BIPHE2 on fertilization and pregnancy cannot presently be performed in women. Also, while our study has proven the effectiveness of 17BIPHE2 as a spermicide for mouse and human sperm in vitro, dosage formulation (e.g. in hydrogel) of 17BIPHE2 still needs to be developed to allow 17BIPHE2 to remain in the vagina/uterine cavity with controlled release for its spermicidal action. WIDER IMPLICATIONS OF THE FINDINGS: Since 17BIPHE2 also exerted bactericidal activity against N. gonorrhoeae at its spermicidal concentration, it is a promising candidate to be developed into a vaginal multipurpose prevention technology agent, thus empowering women against unplanned pregnancies and sexually transmitted infections. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Canadian Institutes of Health Research (PJT 173268 to N.T.). There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Antimicrobial Peptide, LL-37, And Its Potential As An Anti-HIV Agent.

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted.

Cervical Lymphadenopathy in Two Young Women The Same Rare Diagnosis with Different Presentations.

Kikuchi-Fujimoto disease (KFD) is a rare, benign and usually self-limiting disorder that more often affects young women, which is characterized by cervical lymphadenopathy and fever. Clinical presentation may be indistinguishable from other diseases, and its inclusion in the differential diagnosis of lymphoproliferative, infective and autoimmune diseases is essential. An association with systemic lupus erythematosus is acknowledged. We present 2 different cases of 2 young women with KFD; the first case highlights the classic diagnostic features of this rare entity, and the second, the findings when KFD occurs in association with systemic lupus erythematosus. LEARNING POINTS: Fever and cervical lymphadenopathy presenting in a young woman are the main features of KFD.A timely excisional lymph node biopsy is of the utmost importance in establishing a correct diagnosis and in the management of this condition.In most patients with KFD the course of the disease is benign and self-limiting; however, when associated with other conditions (mainly systemic lupus erythematosus) it can follow a more severe evolution.

Cardiac Tamponade after Thrombolysis for Acute Ischemic Stroke A Case with an Excellent Outcome.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the established treatment for acute ischemic stroke and has been highly effective in reducing the neurological deficit. Serious adverse events are not uncommon, with hemorrhage being the major complication. We describe the case of a patient with acute ischemic stroke that also presented with vague cardiac symptoms and was treated with rtPA, which was complicated by a hemopericardium causing cardiac tamponade. Pericardiocentesis was promptly performed, which resulted in rapid resolution of the cardiogenic shock. The patient recovered consciousness within a few minutes. A search of the MEDLINE database shows that this is the first report of cardiac tamponade after rtPA thrombolysis occurring in a patient with no history of recent myocardial infarction or aortic dissection. LEARNING POINTS: Cardiac tamponade is a medical emergency and if not recognized and treated quickly results in cardiogenic shock and death. Hence, it is necessary to be aware that the established treatment for acute ischemic stroke can lead to cardiac tamponade.Cardiac tamponade after rtPA thrombolysis can occur in patients with no history of recent myocardial infarction or aortic dissection.