Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides

Treacher Collins Syndrome with Patent Ductus Arteriosus: A Case Report

Objective: Treacher Collins syndrome or mandibulofacial dysostosis is a rare genetic syndrome characterized by a small mandible and ear anomalies. Some of the patients have congenital heart disease. Case report: A 10-months old female infant with micrognathia, bilateral conductive hearing loss needing hearing aid, and patent ductus arteriosus is presented. Chromosomal study yielded normal karyotype and Treacher Collins syndrome was the first diagnosed by the genetician. The ductus was occluded by a pfm coil. Conclusion: In general, patient affected with Treacher Collins syndrome have no mental or skeletal problems and they can be productive members of the society. So diagnosis and treatment of their congenital heart abnormalities has a greater importance in comparison with patients affected by other genetic syndrome

Treacher Collins Syndrome with Patent Ductus Arteriosus: A Case Report

Objective: Treacher Collins syndrome or mandibulofacial dysostosis is a rare genetic syndrome characterized by a small mandible and ear anomalies. Some of the patients have congenital heart disease. Case report: A 10-months old female infant with micrognathia, bilateral conductive hearing loss needing hearing aid, and patent ductus arteriosus is presented. Chromosomal study yielded normal karyotype and Treacher Collins syndrome was the first diagnosed by the genetician. The ductus was occluded by a pfm coil. Conclusion: In general, patient affected with Treacher Collins syndrome have no mental or skeletal problems and they can be productive members of the society. So diagnosis and treatment of their congenital heart abnormalities has a greater importance in comparison with patients affected by other genetic syndrome

Challenges experienced by clients undergoing assisted reproductive technology in Ghana: An exploratory descriptive study

Objective: To explore the experiences of clients accessing assisted reproductive technology (ART) services in selected health facilities in Greater Accra, Ghana. Methods: An exploratory, descriptive, qualitative design using a purposive sampling technique was employed. Overall, 12 women and six men participated in the study. In‐depth interviews were conducted using a semi‐structured interview guide. The Braun and Clarke (2006) procedure for data analysis was followed. Data collection spanned 9 months (January to October 2017). Results: Five major challenges were identified that were commonly experienced by our participants at every phase of the ART treatment, including the high cost of ART treatment, the long distance to treatment centers, drug treatment challenges, disturbances in daily routine and work, and anxiety about pregnancy outcome. Conclusion: Given the emotional and psychological challenges reported by the participants in the present study, an integration of counseling units in the ART centers is recommended, manned by qualified personnel such as clinical psychologists and counselors to support clients at every stage of the treatment. Also, given the high cost of ART services, as reflected in the participants’ views, it is recommended that private health insurance companies fund some aspect of ART services, such as laboratory investigations and medications