scholarly journals Factors affecting the physical stability (aggregation) of peptide therapeutics

2017 ◽  
Vol 7 (6) ◽  
pp. 20170030 ◽  
Author(s):  
Karolina L. Zapadka ◽  
Frederik J. Becher ◽  
A. L. Gomes dos Santos ◽  
Sophie E. Jackson
Keyword(s):  
Current Knowledge ◽  
Physical Stability ◽  
Therapeutic Agents ◽  
Chemical Degradation ◽  
Physical Parameters ◽  
Net Charge ◽  
Factors Affecting ◽  
Surfaces And Interfaces ◽  
Development Pipeline ◽  
Self Association

The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use. Here, we review the numerous factors that influence the physical stability of peptides including both intrinsic and external factors, wherever possible illustrating these with examples that are of therapeutic interest. The effects of sequence, concentration, pH, net charge, excipients, chemical degradation and modification, surfaces and interfaces, and impurities are all discussed. In addition, the effects of physical parameters such as pressure, temperature, agitation and lyophilization are described. We provide an overview of the structures of aggregates formed, as well as our current knowledge of the mechanisms for their formation.

scholarly journals Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Mija Marinković ◽  
Matilda Šprung ◽  
Maja Buljubašić ◽  
Ivana Novak
Keyword(s):  
Therapeutic Strategy ◽  
Current Knowledge ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Human Diseases ◽  
The Core ◽  
Future Drug ◽  
Autophagic Activity ◽  
Tumor Types ◽  
Catabolic Process

In the last two decades, accumulating evidence pointed to the importance of autophagy in various human diseases. As an essential evolutionary catabolic process of cytoplasmatic component digestion, it is generally believed that modulating autophagic activity, through targeting specific regulatory actors in the core autophagy machinery, may impact disease processes. Both autophagy upregulation and downregulation have been found in cancers, suggesting its dual oncogenic and tumor suppressor properties during malignant transformation. Identification of the key autophagy targets is essential for the development of new therapeutic agents. Despite this great potential, no therapies are currently available that specifically focus on autophagy modulation. Although drugs like rapamycin, chloroquine, hydroxychloroquine, and others act as autophagy modulators, they were not originally developed for this purpose. Thus, autophagy may represent a new and promising pharmacologic target for future drug development and therapeutic applications in human diseases. Here, we summarize our current knowledge in regard to the interplay between autophagy and malignancy in the most significant tumor types: pancreatic, breast, hepatocellular, colorectal, and lung cancer, which have been studied in respect to autophagy manipulation as a promising therapeutic strategy. Finally, we present an overview of the most recent advances in therapeutic strategies involving autophagy modulators in cancer.

scholarly journals SEQUENTIAL THERAPY OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: NEW POSSIBILITIES

2018 ◽  
Vol 14 (3) ◽  
pp. 120-127 ◽  
Author(s):  
A. S. Markova ◽  
V. B. Matveev ◽  
B. M. Nazranov
Keyword(s):  
Prostate Cancer ◽  
Sequential Therapy ◽  
Therapeutic Agents ◽  
Continuous Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Standards ◽  
Factors Affecting ◽  
Castration Resistant ◽  
Line Therapy ◽  
Significant Factors

Currently, doctors have at their disposal a number of drugs prolonging life of patients with castration-resistant prostate cancer (CRPC). The majority is approved for use as the 1st line therapy and, in absence of direct comparison, is considered potentially equally effective. Patients with CRPC need continuous treatment for suppression of disease progression resulting in sequential use of therapeutic agents. Modern standards and recommendations do not provide a clear algorithm for prescription, therefore an individual approach is necessary taking in account various factors of a particular case ranging from previous therapies to patients’ preferences. This article considers the most significant factors affecting CRPC therapy selection and ways of therapy optimization in compliance with the established treatment standards and taking into account the list of drugs approved for use in Russia.

Nurses’ attitudes toward female sex workers: A qualitative study

2020 ◽  
pp. 096973302096149
Author(s):  
Haixia Ma ◽  
Alice Yuen Loke
Keyword(s):  
Hong Kong ◽  
Qualitative Study ◽  
Sex Workers ◽  
Female Sex Workers ◽  
Current Knowledge ◽  
Healthcare Services ◽  
Major Barrier ◽  
Factors Affecting ◽  
Individual Interviews ◽  
Female Sex

Background: Stigma is considered a major barrier to accessing healthcare services by female sex workers. Current knowledge of nurses’ attitudes appears to imply a stigma toward female sex workers. But in-depth understanding of their perceptions is scarce. Furthermore, factors that inform a conceptual understanding of how this occurs are lacking. Objectives: The study aimed to explore nurses’ attitudes toward female sex workers and factors affecting caring for female sex workers. Research design: This was a qualitative study. A content analysis approach was adopted in analyzing the data. Participants and research context: Thirty-three practicing nurses participated in seven semi-structured focus group interviews and three key informants participated in three individual interviews in Hong Kong. Ethical considerations: This study was approved by the Ethics Committee of one university in Hong Kong. Findings: The findings revealed three themes: (1) accept, stigmatize, or against sex work; (2) reluctance, hesitation, or willingness to care for female sex workers; and (3) factors affecting the care of female sex workers. Discussion and conclusion: This study found that nurses held different attitudes toward female sex workers, and they experienced feelings of reluctance, hesitation, or willingness to care for female sex workers. Multi-level factors could affect their level of comfort of caring for female sex workers. Intervention should be developed to encourage health professionals to examine their personal views toward female sex workers introspectively, how their attitude may have affected the provision of quality services, and to enhance the provision of sensitive non-discriminative services to female sex workers.

scholarly journals The Radiostability of Meropenem Trihydrate in Solid State

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2738 ◽  
Author(s):  
Karolina Kilińska ◽  
Judyta Cielecka-Piontek ◽  
Robert Skibiński ◽  
Daria Szymanowska ◽  
Andrzej Miklaszewski ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Solid State ◽  
Physical Stability ◽  
Chemical Degradation ◽  
Beam Radiation ◽  
Promising Alternative ◽  
X Ray ◽  
Lactam Ring ◽  
Ft Ir ◽  
Hydroxyethyl Group

The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of β-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

scholarly journals Pork: profile of the West of Paraná consumers and physical evaluation of chop

2017 ◽  
Vol 38 (6) ◽  
pp. 3563
Author(s):  
Rosana Aparecida da Silva-Buzanello ◽  
Daneysa Lahis Kalschne ◽  
Silmara Maisa Heinen ◽  
Claudete Pertum ◽  
Alexia Francielli Schuch ◽  
...  
Keyword(s):  
Meat Quality ◽  
Storage Conditions ◽  
Absorption Capacity ◽  
Physical Parameters ◽  
Exploratory Research ◽  
Factors Affecting ◽  
Pig Farming ◽  
Consumption Index ◽  
The One ◽  
Processing And Storage

Pork consumption in Brazil is still low despite its productive importance. Relevant issues such as swine breeding, meat quality, and evaluation of aspects and attributes considered important by pork consumers at the time of purchase allows identifying consumer market demands. Moreover, physical parameters evaluation or pork cuts are suggested to certify the meat quality. The aim of this study was to identify the current situation of pig farming and determine the main aspects considered by consumers when buying pork in the Western region of Paraná state, Brazil. Furthermore, the physical properties of five pork chop brands marketed in the region were determined. Initially, an exploratory research was conducted involving ten pig farming sector professionals. This research allowed identifying that professionals understand the factors affecting meat quality and that some municipalities in the region are beyond their absorption capacity for pig production market. A descriptive research involving one hundred pork consumers showed that, although most prefer beef, 41% reported to consume pork 2 to 3 times a week. Pork chops and ribs are the preferred cuts, either fried or roasted. Details such as expiration date and federal inspection register were considered the most important aspects at the time of purchase, while price was the least important one. The meat color was the most mentioned sensory attribute. The physical analyses of five pork chop brands showed no pH difference (p > 0.05), water holding capacity, and cooking loss results, distinctive from the one observed for color (L*, a* and b*) and shearing force, which showed differences among the brands (p ? 0.05). Comparing pH and L*, it can be suggested that two brands showed normal meat characteristics, one DFD meat (pH > 6.0 and L* < 45), and other two brands PSE (pH < 5.8 and L* > 50). The research contributed to identifying features considered important by pork consumers, suggesting strategic actions to achieve greater preference and consumption index. The evaluation of physical parameters showed there is variability involved in pork chop quality as the samples were obtained from commercially different origins and under different processing and storage conditions.

scholarly journals An Initial Model of Trust in Chatbots for Customer Service—Findings from a Questionnaire Study

2019 ◽  
Vol 31 (3) ◽  
pp. 317-335 ◽  
Author(s):  
Cecilie Bertinussen Nordheim ◽  
Asbjørn Følstad ◽  
Cato Alexander Bjørkli
Keyword(s):  
Customer Service ◽  
Current Knowledge ◽  
Interactive Systems ◽  
Questionnaire Study ◽  
Initial Model ◽  
Related Factors ◽  
Factors Affecting ◽  
Propensity To Trust ◽  
Brand Perception ◽  
Current Knowledge Base

Abstract Chatbots are predicted to play a key role in customer service. Users’ trust in such chatbots is critical for their uptake. However, there is a lack of knowledge concerning users’ trust in chatbots. To bridge this knowledge gap, we present a questionnaire study (N = 154) that investigated factors of relevance for trust in customer service chatbots. The study included two parts: an explanatory investigation of the relative importance of factors known to predict trust from the general literature on interactive systems and an exploratory identification of other factors of particular relevance for trust in chatbots. The participants were recruited as part of their dialogue with one of four chatbots for customer service. Based on the findings, we propose an initial model of trust in chatbots for customer service, including chatbot-related factors (perceived expertise and responsiveness), environment-related factors (risk and brand perceptions) and user-related factors (propensity to trust technology). RESEARCH HIGHLIGHTS We extend the current knowledge base on natural language interfaces by investigating factors affecting users’ trust in chatbots for customer service. Chatbot-related factors, specifically perceived expertise and responsiveness, are found particularly important to users’ trust in such chatbots, but also environment-related factors such as brand perception and user-related factors such as propensity to trust technology. On the basis of the findings, we propose an initial model of users’ trust chatbots for customer service.

scholarly journals Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel/Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 501 ◽  
Author(s):  
Monica Boffito ◽  
Carlotta Pontremoli ◽  
Sonia Fiorilli ◽  
Rossella Laurano ◽  
Gianluca Ciardelli ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Chemical Degradation ◽  
Burst Release ◽  
Injectable Hydrogels ◽  
Micro Particles ◽  
Custom Made ◽  
Thermosensitive Hydrogels ◽  
Polyurethane Hydrogel ◽  
Over Time ◽  
Incipient Wetness Method

Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% w/w). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3–5 min). Cu2+ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu2+, respectively). Additionally, released Cu2+ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.

Understanding the Factors Affecting Employees’ Motivation to Engage in Co-Creation in the Banking Industry

2020 ◽  
Vol 17 (02) ◽  
pp. 2050015 ◽  
Author(s):  
Anna Feldmann ◽  
Frank Teuteberg
Keyword(s):  
Current Knowledge ◽  
Qualitative Interviews ◽  
Business Environment ◽  
Point Of View ◽  
Integrative Model ◽  
Factors Affecting ◽  
Motivation Factors ◽  
Business To Consumer ◽  
Motivation To Participate

Increasing digitalization and new technological possibilities also entail substantial changes for working methods in the B2B (business-to-business) environment in banking. In this context, the concept of co-creation is critical. Although this concept and the motivation factors behind it have been thoroughly investigated in the B2C (business-to-consumer) sector, only a few research results exist for the B2B context. This study aims to bridge the current knowledge gap and investigate individuals’ motivation to participate in B2B co-creation. By using a case study and qualitative interviews, this study focuses on two aspects: (a) It reveals how a co-creation measure is used in practice in the B2B environment; and (b) it provides information on the motivation factors and outcome from the point of view of the participants in the B2B co-creation project. The paper concludes with an integrative model of the main motivation factors behind B2B co-creation and their effects.

Defense peptides: recent developments

2015 ◽  
Vol 6 (4) ◽  
pp. 237-251 ◽  
Author(s):  
Małgorzata Cytryńska ◽  
Agnieszka Zdybicka-Barabas
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Membrane Lipid ◽  
Factors Affecting ◽  
Natural Defense ◽  
Secreted Factors ◽  
Recent Developments ◽  
Extracellular Proteinases ◽  
Defense Peptides ◽  
Conventional Antibiotics

AbstractDefense peptides are small amphipathic molecules that exhibit antimicrobial, antitumor, antiviral, and immunomodulatory properties. This review summarizes current knowledge on the mechanisms of antimicrobial activity of cationic and anionic defense peptides, indicating peptide-based as well as microbial cell-based factors affecting this activity. The peptide-based factors include charge, hydrophibicity, and amphipathicity, whereas the pathogen-based factors are membrane lipid composition, presence of sterols, membrane fluidity, cell wall components, and secreted factors such as extracellular proteinases. Since defense peptides have been considered very promising molecules that could replace conventional antibiotics in the era of drug-resistant pathogens, the issue of microbial resistance to antimicrobial peptides (AMPs) is addressed. Furthermore, selected approaches employed for optimization and de novo design of effective AMPs based on the properties recognized as important for the function of natural defense peptides are presented.

scholarly journals Sensitivity analysis of crude oil’s physical properties to total freezing time

2020 ◽  
Vol 24 (6 Part A) ◽  
pp. 3735-3747
Author(s):  
Yang Liu ◽  
Ying Xu ◽  
Xiaoyan Liu ◽  
Qinglin Cheng ◽  
Xin Nie ◽  
...  
Keyword(s):  
Heat Transfer ◽  
Crude Oil ◽  
Solution Method ◽  
Convection Heat Transfer ◽  
Orthogonal Test ◽  
Maximum Temperature ◽  
Physical Parameters ◽  
Freezing Time ◽  
Factors Affecting ◽  
Main Factors

The physical parameters of crude oil are one of the main factors affecting the heat transfer of phase change. A mathematical model for a hot oil overhead pipeline was established, taking latent heat impact, the non-Newtonian properties of crude oil, and nature convection heat transfer into account. Compared with the experimental data, the model and the solution method were correct. A criterion was made to estimate the crude oil total freezing in a pipeline by tracking the change trajectory of the maximum temperature point. The effects of the crude oil with average properties on the total freezing time in a pipeline were analyzed, and the sensitivity of the different influencing factors was investigated by orthogonal test.

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