Analytics of the therapeutic peptide aviptadil by sheathless CE-MS and comparison with nanoRP-HPLC-MS.

Billy Bennett

Purification and quality control of therapeutic peptides is often performed by one single method, RP-HPLC. As usage of an orthogonal technique is highly advisable for quality assurance, capillary electrophoresis (CE) employing a coated capillary coupled via a sheathless interface to a mass spectrometer was applied in parallel. The basic therapeutic peptide aviptadil served as a model substance to study the impurity profiles revealing 15 detectable impurities using CE-MS, two were detected by an appropriate nanoRP-HPLC-MS method. None of the impurities detected by CE were observed in LC and vice versa.

The LOD in CE-MS was determined in the base peak electropherogram at ∼1fmol, a value 2500 times smaller than the LOD found in nanoRP-HPLC-MS (3pmol). In nanoRP-HPLC-MS only 0.2% of the extrapolated CE-MS signal for a 25ng aviptadil load was observed. We conclude that both, the LOD as well as the impurity profile of aviptadil, as analyzed by nanoRP-HPLC are influenced by both, the ligand-derivatized silica matrix and the flow-rate. Peptides may disappear completely and their variable emergence may lead to the determination of incorrect ratios as present in the sample.

Aviptadil (Senatek)

Aviptadil is an injectable formulation of vasoactive intestinal polypeptide (VIP) in combination with the adrenergic drug phentolamine. Aviptadil in combination with phentolamine and sexual stimulation, is expected to provide a new and effective alternative for erectile dysfunction (ED) patients that is essentially free of the troublesome side effects and cumbersome delivery methods which limit the use of other pharmacologic preparations. Aviptadil can be delivered using Senetek’s novel and patented autoinjector (Reliaject), which renders the self-injection process exceptionally easy, unobtrusive to perform and helps ensure accurate, safe delivery of the medication [306380]. In July 1997, Senetek filed a PLA with the Danish Medicines Authority [253591] and its third PLA in Ireland for the treatment of moderate-to-severe, organic-based ED [255084]. In September 1997, Senetek filed PLAs seeking approval to market aviptadil in Switzerland, South Africa and New Zealand 1263505]; by April 2000, it had been approved in New Zealand [361039].

All clinical trials were placed on hold in August 1999 after the FDA advised the MCA of safety concerns regarding a competitor’s phentolamine mesylate product (Vasomax; Zonagen Inc/Schering-Plough Corp). At this time, the activities to support the registration of aviptadil in the EU were ongoing and were not impacted by the clinical hold [336510]. In March 2000, after review by an independent clinical pharmacotoxicologist company employed by Senetek, the carcinogenicity observed in animal models was deemed to have no relevance as an indicator of carcinogenic risk in humans.

This information was passed to the MCA along with an extensive review of all prior company studies and the medical literature supporting the efficacy and safety of phentolamine mesylate [361039]. In July 2000, the FDA upgraded the status of the aviptadil IND to a partial clinical hold, allowing human studies to be conducted in the US with a limited duration of 3 months and total number of doses not exceeding three per week. The FDA also recommended that Senetek conduct a two-year rodent study of aviptadil as a result of previously reported brown adipose tissue proliferations observed in the course of a competitor’s rodent study in which phentolamine mesylate was administered daily [373086].

In August 2000, the MCA lifted the hold on trials stating the findings do not represent a significant carcinogenic risk in man [378615]. In October 2000, marketing approval in the UK was granted by the MCA. Regulatory filings in other European countries are underway to seek pan-European approval for aviptadil under the Mutual Recognition Process [385477].

Evaluating the Capacitive Response in Metal Halide Perovskite Solar Cells

The perovskites solar cells (PSCs) is composed of multifaceted device architecture and involve complex charge extraction (both electronic and ionic), this makes the task demanding to unlock the origin of the different physical process that occurs in a PSC. The capacitance in PSCs depends on several external perturbations including frequency, illumination, temperature, applied bias, and importantly on the interface modification of perovskites/charge selective contact. Arguably, different features including interfacial and bulk; ionic, and electronic charge transport in PSCs occur at different time scales. Capacitance spectroscopy is a prevailing technique to unravel the various physical phenomenon that occurs in a PSC at different time scales. A deeper knowledge of the capacitive response of a PSCs is essential to understand the charge carrier kinetics and unlock the device physics. This work highlights the capacitive response of PSCs and its application to unlock the device physics which is essential for the further optimization and improvement of the device performance.

Optimizing human-centered AI for healthcare in the Global South

Over the past 60 years, artificial intelligence (AI) has made significant progress, but most of its benefits have failed to make a significant impact within the Global South. Current practices that have led to biased systems will prevent AI from being actualized unless significant efforts are made to change them. As technical advances in AI and an interest in solving new problems lead researchers and tech companies to develop AI applications that target the health of marginalized communities, it is crucially important to study how AI can be used to empower those on the front lines in the Global South and how these tools can be optimally designed for marginalized communities. This perspective examines the landscape of AI for healthcare in the Global South and the evaluations of such systems and provides tangible recommendations for AI practitioners and human-centered researchers to incorporate in the development of AI systems for use with marginalized populations.

Ying Yang 1 engagement in brain pathology

Herein, we discuss data concerning the involvement of transcription factor Yin Yang 1 (YY1) in the development of brain diseases, highlighting mechanisms of its pathological actions. YY1 plays an important role in the developmental and adult pathology of the nervous system. YY1 is essential for neurulation as well as maintenance and differentiation of neuronal progenitor cells and oligodendrocytes regulating both neural and glial tissues of the brain. Lack of a YY1 gene causes many developmental abnormalities and anatomical malformations of the central nervous system (CNS).

Once dysregulated, YY1 exerts multiple neuropathological actions being involved in the induction of many brain disorders like stroke, epilepsy, Alzheimer’s and Parkinson’s diseases, autism spectrum disorder, dystonia, and brain tumors. Better understanding of YY1’s dysfunction in the nervous system may lead to the development of novel therapeutic strategies related to YY1’s actions.

An insight on microbial degradation of benzo[a]pyrene: current status and advances in research

Benzo[a]pyrene (BaP) is a high molecular weight polycyclic aromatic hydrocarbon produced as a result of incomplete combustion of organic substances. Over the years, the release of BaP in the atmosphere has increased rapidly, risking human lives. BaP can form bonds with DNA leading to the formation of DNA adducts thereby causing cancer. Therefore addressing the problem of its removal from the environment is quite pertinent though it calls for a very cumbersome and tedious process owing to its recalcitrant nature. To resolve such issues many efforts have been made to develop physical and chemical technologies of BaP degradation which have neither been cost-effective nor eco-friendly.

Medrysone
HY-B1076	MedChemExpress	100mg	142.8 EUR
Medronic acid
HY-108309	MedChemExpress	10mM/1mL	135.6 EUR
Medetomidine
HY-17034	MedChemExpress	50mg	391.2 EUR
Medicagenic acid
HY-N2472	MedChemExpress	10mg	384 EUR
Olmesartan (medoxomil)
HY-17005	MedChemExpress	50mg	176.4 EUR
Azilsartan (medoxomil)
HY-14736	MedChemExpress	10mM/1mL	267.6 EUR
Medetomidine (hydrochloride)
HY-17034B	MedChemExpress	50mg	391.2 EUR
Medroxyprogesterone (acetate)
HY-B0469	MedChemExpress	10mM/1mL	151.2 EUR
Azilsartan (medoxomil monopotassium)
HY-17458	MedChemExpress	50mg	1350 EUR
Thevetiaflavone
HY-N1157	MedChemExpress	5mg	1093.2 EUR
Taraxasterol
HY-N1178	MedChemExpress	5mg	338.4 EUR
Syzalterin
HY-N1187	MedChemExpress	5mg	1093.2 EUR
Stigmasterol glucoside
HY-N1200	MedChemExpress	5mg	1634.4 EUR
Apigenin
HY-N1201	MedChemExpress	10mM/1mL	135.6 EUR
Squalene
HY-N1214	MedChemExpress	5mg	129.6 EUR
Scabertopin
HY-N1247	MedChemExpress	5mg	955.2 EUR
Seneciphyllinine
HY-N1283	MedChemExpress	5mg	2029.2 EUR
Reynoutrin
HY-N1354	MedChemExpress	10mg	418.8 EUR
Salvianolic acid B
HY-N1362	MedChemExpress	25mg	391.2 EUR

Microbial degradation of BaP, on the other hand, has gained much attention due to added advantage of the high level

of microbial diversity enabling great potential to degrade the substance without impairing environmental sustainability. Microorganisms produce enzymes like oxygenases, hydrolases and cytochrome P450 that enable BaP degradation. However, microbial degradation of BaP is restricted due to several factors related to its bio-availability and soil properties. Technologies like bio-augmentation and bio-stimulation have served to enhance the degradation rate of BaP. Besides, advanced technologies such as omics and nano-technology have opened new doors for a better future of microbial degradation of BaP and related compounds.