Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy

NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

Mostafa M Ghorab,1,2 Mansour S Alsaid,1 Maureen Higgins,3 Albena T Dinkova-Kostova,3–5 Abdelaaty A Shahat,1,6 Nehal H Elghazawy,7 Reem K Arafa7,8 1Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Drug Radiation Research, National Center for Radiation Research & Technology, Atomic Energy Authority, Cairo, Egypt; 3Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, UK; 4Department of Medicine, 5Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 6Phytochemistry Department, National Research Center, Dokki, Giza, 7Zewail City of Science and Technology, 8Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt Abstract: The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series. Keywords: Kelch domain, molecular modeling, Keap1/Nrf2, cytoprotection, NQO1 inductio

A new strategy for taste masking of azithromycin antibiotic: development, characterization, and evaluation of azithromycin titanium nanohybrid for masking of bitter taste using physisorption and panel testing studies

Fazli Amin,1 Shahzeb Khan,1,2 Syed Muhammad Hassan Shah,3 Haroon Rahim,3 Zahid Hussain,4 Muhammad Sohail,5 Riaz Ullah,6,7 Mansour S Alsaid,6 Abdelaaty A Shahat6,8 1Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu Natal, Westville 4000, Durban South Africa; 3Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan; 4Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi MARA, Selangor, Malaysia; 5Department of Pharmacy, COMSATS, Abbottabad, Khyber Pakhtunkhwa, Pakistan; 6Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 7Department of Chemistry, Government College Ara Khel FR, Kohat, Khyber Pakhtunkhwa, Pakistan; 8Phytochemistry Department, National Research Centre, Dokki, Giza, Egypt Background: The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue. Purpose of study: The study aimed to mask and evaluate the unpleasant bitter taste of azithro­mycin (AZ) in the dry suspension dosage form by physisorption technique. Materials and methods: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form.Results: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation.Conclusion: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate. Keywords: azithromycin, AZ, titanium dioxide nanoparticles, TNPs, azithromycin–TiO2 nanohybrid, AZN, dissolution, physisorption&nbsp

Experimental and molecular modeling approach to optimize suitable polymers for fabrication of stable fluticasone nanoparticles with enhanced dissolution and antimicrobial activity

Shaimaa Ahmed,1 Thirumala Govender,1 Inamullah Khan,2 Nisar ur Rehman,2 Waqar Ali,2 Syed Muhammad Hassan Shah,3 Shahzeb Khan,4 Zahid Hussain,5 Riaz Ullah,6,7 Mansour S Alsaid6 1Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Department of Pharmacy, COMSATS Institute of Information Technology (CIIT), Abbotabad, 3Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, 4Department of Pharmacy, University of Malakand Dir (Lower), Chakdara, Khyber Pakhtunkhwa, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi Mara, Puncak Alam, Selangor, Malaysia; 6Department of Pharmacognosy and Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 7Department of Chemistry, Government College Ara Khel FR, Kohat, Khyber Pakhtunkhwa, Pakistan Background and aim: The challenges with current antimicrobial drug therapy and resistance remain a significant global health threat. Nanodrug delivery systems are playing a crucial role in overcoming these challenges and open new avenues for effective antimicrobial therapy. While fluticasone (FLU), a poorly water-soluble corticosteroid, has been reported to have potential antimicrobial activity, approaches to optimize its dissolution profile and antimicrobial activity are lacking in the literature. This study aimed to combine an experimental study with molecular modeling to design stable FLU nanopolymeric particles with enhanced dissolution rates and antimicrobial activity. Methods: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles. Results and conclusion: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C–8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P<0.05) compared to the unprocessed counterpart. The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against gram-positive bacteria compared to the unprocessed FLU and positive control. Keywords: fluticasone, nanoparticles, drug delivery systems, antimicrobial, molecular modeling, molecular dynamic

Chemical Composition, Antioxidant and Anti-bacterial Potential of Essential Oil of Medicinal plant Isodon rugosus

Isodon rugosus is a medicinally valuable herb containing a variety of important secondary metabolites and essential oil with important chemical constituents of pharmaceutical precursors. The active components of volatile oil of I. rugosus were analyzed using GC-MS. Anti-oxidant potential of the oil was assessed with 2, 2-diphenyl-1-picrylhydrazyl (DPPH). Anti-bacterial power of the essential oil accessed disc diffused method. A total of 19 constituents were quantified and identified with different concentrations in essential oil. Among which Caryophyllene oxide was 28.99 %. Limonene oxide cis was 26.52 %, (Z, E)-Farnesol was 17.34 %, followed by 1-erpinen-4-ol 3.33 %, o-Cymene 2.04 while the concentrations of rest of constituents were between 1.11 to 0.2 %. The investigation showed that the essential oil of I. rugosus possessed significant antibacterial and antioxidant potentia